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BACKGROUND: Primary gliosarcoma is a rare form of malignant central nervous system (CNS) tumor, with limited understanding regarding its prognostic determinants and effective therapeutic interventions. METHODS: The medical records of patients diagnosed with gliosarcoma at Tangdu Hospital between March 2011 and June 2023 were retrospectively analyzed in this study. Patients with a prior history of glioma or those who received preoperative chemoradiotherapy were excluded. Survival analyses were conducted using Kaplan-Meier and Cox regression analysis. RESULTS: A total of 77 patients were included in the final analysis with a median age of 57 years (range 13-83). The predominant symptom leading to diagnosis was headache, and the temporal lobe was the most frequently affected site. Univariate analysis revealed that age ≤ 65 years, complete resection, Ki67 ≤ 25%, postoperative Karnofsky Performance Status (KPS) ≥ 70, adherence to the Stupp protocol, and additional active therapy upon relapse were associated with enhanced survival. Furthermore, multivariate analysis identified complete resection, aged ≤ 65 years, Stupp protocol treatment, and active therapy following relapse were independent predictors of overall survival (OS). Notably, one patient experienced subcutaneous metastasis during treatment. CONCLUSIONS: The present study's findings suggest that optimal management of primary gliosarcoma entails maximal safe resection, combined with adjuvant radiotherapy and chemotherapy with temozolomide, followed by salvage therapy in case of recurrence. However, the risk of metastases should be carefully monitored during the treatment course.
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OBJECTIVE: To explore mortality risk factors and to construct an online nomogram for predicting in-hospital mortality in traumatic brain injury (TBI) patients receiving invasive mechanical ventilation (IMV) in intensive care unit (ICU). METHODS: We retrospectively analysed TBI patients on IMV in ICU from MIMIC-â £ database and two hospitals. Least Absolute Shrinkage and Selection Operation (LASSO) regression and multiple logistic regression were used to detect predictors of in-hospital mortality and to construct an online nomogram. The predictive performance of nomogram was evaluated using area under the receiver operating characteristic curves (AUC), calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). RESULTS: 510 from MIMIC-â £ database were enrolled for nomogram construction (80%, n=408) and internal validation (20%, n=102). 185 from two hospitals were enrolled for external validation. LASSO-Logistic regression revealed predictors of in-hospital mortality among TBI patients on IMV in ICU included Glasgow Coma Scale (GCS) after ICU admission, Acute Physiology Score â ¢ (APS â ¢) after ICU admission, neutrophil and lymphocyte ratio after IMV, blood urea nitrogen after IMV, arterial serum lactate after IMV, and in-hospital tracheotomy. The AUC, calibration curves, DCA, and CIC indicated the nomogram had good discrimination, calibration, clinical benefit, and applicability. The multi-model comparisons revealed the nomogram had higher AUC than GCS, APS â ¢, and Simplified Acute Physiology Score â ¡. CONCLUSION: We constructed and validated an online nomogram based on routinely recorded factors at admission to ICU and at the beginning of IMV to target prediction of in-hospital mortality among TBI patients on IMV in ICU.
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OBJECTIVE: To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram. METHODS: Data from elderly individuals (age ≥65 years) histologically diagnosed with brain glioma were sourced from the Surveillance, Epidemiology, and End Results (SEER) database. The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio. Additionally, data obtained from Tangdu Hospital constituted an external validation cohort for the study. The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis, enabling the construction of a nomogram. Model performance was evaluated using C-index, ROC curves, calibration plot and decision curve analysis (DCA). RESULTS: A cohort of 20 483 elderly glioma patients was selected from the SEER database. Five prognostic factors (age, marital status, histological type, stage, and treatment) were found to significantly impact overall survival (OS) and cancer-specific survival (CSS), with tumor location emerging as a sixth variable independently linked to CSS. Subsequently, nomogram models were developed to predict the probabilities of survival at 6, 12, and 24 months. The assessment findings from the validation queue indicate a that the model exhibited strong performance. CONCLUSION: Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients. They can potentially assist in risk stratification and clinical decision-making.
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Brain Neoplasms , Glioma , Nomograms , SEER Program , Humans , Glioma/mortality , Glioma/pathology , Aged , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Female , Male , Risk Factors , Prognosis , Aged, 80 and over , ROC CurveABSTRACT
Severe traumatic brain injury (sTBI) is a prominent contributor to both morbidity and mortality in the elderly population. The monitoring of intracranial pressure (ICP) is crucial in the management of sTBI patients. Nevertheless, the appropriate timing for the placement of ICP monitor in elderly sTBI patients remains uncertain. To determine the optimal timing for the placement of ICP monitor in elderly sTBI patients, in this retrospective cohort study, we collected data from elderly patients (> 65 years) who suffered sTBI and received ICP monitors at Tangdu Hospital, The Fourth Military Medical University, between January 2011 and December 2021. To examine the relationship between the time of ICP monitor placement and in-hospital mortality, we conducted a multi-variate-adjusted restricted cubic spline (RCS) analysis. Additionally, logistic regression analysis was applied to further analyze the influencing factors contributing to early or late ICP monitor placements. A total of 283 eligible elderly TBI patients were included in the current analysis. The in-hospital mortality rate was 73 out of 283 (26%). The RCS analysis demonstrated an inverted U-shaped curve in the relationship between the timing of ICP monitor placement and in-hospital mortality. For the elderly sTBI patient cohort, 6 h was identified as the crucial moment for the treatment strategy. In addition, the protective time window for ICP placement was less than 4.92 h for the GCS 3-5 group, and less than 8.26 h for the GCS 6-8 group. However, the clinical benefit of ICP placement decreased gradually over time. The relationship between ICP placement and in-hospital mortality was non-linear, exhibiting an inverted U-shaped curve in elderly patients with sTBI. For elderly patients with sTBI, early (≤ 6 h) ICP placement was associated with reduced in-hospital mortality. The clinical benefit of ICP placement decreased beyond the optimal time window.
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OBJECTIVE: This study aims to identify risk factors for central nervous system (CNS) infection in elderly patients hospitalized with traumatic brain injury (TBI) and to develop a reliable predictive tool for assessing the likelihood of CNS infection in this population. METHOD: We conducted a retrospective study on 742 elderly TBI patients treated at Tangdu Hospital, China. Clinical data was randomly split into training and validation sets (7:3 ratio). By conducting univariate and multivariate logistic regression analysis in the training set, we identified a list of variables to develop a nomogram for predicting the risk of CNS infection. We evaluated the performance of the predictive model in both cohorts respectively, using receiver operating characteristics curves, calibration curves, and decision curve analysis. RESULTS: Results of the logistic analysis in the training set indicated that surgical intervention (P = 0.007), red blood cell count (P = 0.019), C-reactive protein concentration (P < 0.001), and cerebrospinal fluid leakage (P < 0.001) significantly predicted the occurrence of CNS infection in elderly TBI patients. The model constructed based on these variables had high predictive capability (area under the curve-training = 0.832; area under the curve-validation = 0.824) as well as clinical utility. CONCLUSIONS: A nomogram constructed based on several key predictors reasonably predicts the risk of CNS infection in elderly TBI patients upon hospital admission. The model of the nanogram may contribute to timely interventions and improve health outcomes among affected individuals.
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Brain Injuries, Traumatic , Central Nervous System Infections , Aged , Humans , Nomograms , Retrospective Studies , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/diagnosis , Risk FactorsABSTRACT
OBJECTIVE: The classification of central nervous system (CNS) tumors has changed greatly. The Central Brain Tumor Registry of the United States (CBTRUS) and other institutions have analyzed the incidence rate and characteristics of primary CNS tumors. However, there are limited studies analyzing the incidence rate and characteristics of CNS tumors in China. To better understand CNS tumors in China, we summarized all primary CNS tumors diagnosed pathologically in a single center from 2003 to 2019. METHODS: All patients with primary CNS tumors who underwent neurosurgery at our hospital from January 2003 to December 2019 were included in this study. The data were collected from the hospital information system, including diagnosis time, age, gender, anatomic sites, and pathologic results. RESULTS: A total of 17,226 cases of primary CNS tumors were retrospectively analyzed in this study. Among all cases, the major tumor types included meningiomas, tumors of neuroepithelial tissue, and pituitary adenomas. Most tumors of neuroepithelial tissue were glioblastoma and astrocytoma. Most tumors of neuroepithelial tissue were located in the frontal lobe. However, grade 4 tumors of neuroepithelial tissue were more common in the temporal lobe. The median age of all patients was 46 years. The incidence of CNS tumors was higher in women than in men. CONCLUSIONS: Based on this data set, we analyzed various parameters of CNS tumors and found that grade 4 tumors of neuroepithelial tissue were more common in the temporal lobe, which were rarely reported in previous articles.
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Brain Neoplasms , Central Nervous System Neoplasms , Meningeal Neoplasms , Male , Humans , Female , United States , Middle Aged , Retrospective Studies , Central Nervous System Neoplasms/epidemiology , Central Nervous System Neoplasms/surgery , Central Nervous System Neoplasms/diagnosis , Brain Neoplasms/epidemiology , Brain Neoplasms/pathology , China/epidemiology , IncidenceABSTRACT
Objective: Traumatic brain injury (TBI) is a global social, economic, and health challenge that is associated with premature death and long-term disability. In the context of rapid development of urbanization, the analysis of TBI rate and mortality trend could provide abundant diagnosis and treatment suggestions, which helps to form future reference on public health strategies. Methods: In this study, as one of major neurosurgical centers in China, we focused on the regime shift of TBI based on 18-year consecutive clinical data and evaluated the epidemiological features. In our current study, a total of 11,068 TBI patients were reviewed. Results: The major cause of TBI was road traffic injuries (44.%), while the main type of injury was cerebral contusion (n = 4,974 [44.94%]). Regarding to temporal changes, a decreasing trend in TBI incidence for patients under 44 years old was observed, while an increasing trend for those aged over 45 years was indicated. Incidences of RTI and assaults decreased, while ground level fall presented increasing incidences. The total number of deaths was 933 (8.43%), with a decreasing trend in overall mortality since 2011. Age, cause of injury, GCS at admission, Injury Severity Score, shock state at admission, trauma-related diagnoses and treatments were significantly associated with mortality. A predictive nomogram model for poor prognosis was developed based on patient's GOS scores at discharge. Conclusions: The trends and characteristics of TBI patients changed with rapid development of urbanization in the past 18 years. Further larger studies are warranted to verify its clinical suggestions.
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Post-neurosurgical infections caused by multidrug-resistant Enterobacterales are difficult to treat due to limited therapeutic options. Ceftazidime-avibactam (CAZ-AVI), a combination of cephalosporin and a novel ß-lactamase inhibitor, has exhibited potential activity against multi/extensive drug-resistant (MDR/XDR) gram-negative bacilli. Several reports have described the successful treatment of central infections caused by MDR/XDR Pseudomonas aeruginosa or Enterobacterales. However, data on the efficacy and effective drug distribution of CAZ-AVI in the central nervous system (CNS), particularly in children, are lacking. We report a case of a 4-year-old girl with post-neurosurgical meningitis and abscess caused by extended-spectrum ß-lactamase-producing Escherichia coli successfully treated with CAZ-AVI. CAZ-AVI therapeutic drug monitoring was performed to evaluate its efficacy and effective drug distribution in the CNS. We measured CAZ (15.6, 7.1, and 3.5 µg/mL) and AVI (4.0, 2.1, and 1.2 µg/mL) in cerebrospinal fluid (CSF) samples obtained 3, 5, and 7 h after the administration of the 15th CAZ-AVI dose (2.5 g, q8h, iv), respectively. We also measured CAZ (57.0 and 25.8 µg/mL) and AVI (11.3 and 4.5 µg/mL) in serum samples obtained 3 and 5 h after the administration, respectively. CAZ-AVI achieved an adequate CSF concentration throughout the drug interval. Our case provides evidence for using CAZ-AVI to treat CNS infections.
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Objective: Awake craniotomy with intraoperative brain functional mapping effectively reduces the potential risk of neurological deficits in patients with glioma invading the eloquent areas. However, glioma patients frequently present with impaired neurocognitive function. The present study aimed to investigate the neurocognitive and functional outcomes of glioma patients after awake brain mapping and assess the experience of a tertiary neurosurgical center in China over eight years. Methods: This retrospective study included 80 patients who underwent awake brain mapping for gliomas invading the eloquent cortex between January 2013 and December 2021. Clinical and surgical factors, such as the extent of resection (EOR), perioperative Karnofsky Performance Score (KPS), progression-free survival (PFS), and overall survival (OS), were evaluated. We also used the Montreal Cognitive Assessment (MoCA) to assess the neurocognitive status changes. Results: The most frequently observed location of glioma was the frontal lobe (33/80, 41.25%), whereas the tumor primarily invaded the language-related cortex (36/80, 45%). Most patients had supratotal resection (11/80, 13.75%) and total resection (45/80, 56.25%). The median PFS was 43.2 months, and the median OS was 48.9 months in our cohort. The transient (less than seven days) neurological deficit rate was 17.5%, whereas the rate of persistent deficit (lasting for three months) was 15%. At three months of follow-up, most patients (72/80, 90%) had KPS scores > 80. Meanwhile, compared to the preoperative baseline tests, the changes in MoCA scores presented significant improvements at discharge and three months follow-up tests. Conclusion: Awake brain mapping is a feasible and safe method for treating glioma invading the eloquent cortex, with the benefit of minimizing neurological deficits, increasing EOR, and extending survival time. The results of MoCA test indicated that brain mapping plays a critical role in preserving neurocognitive function during tumor resection.
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Background: CNS tumors, particularly gliomas, are associated with a high rate of disability and lethality, and are typically diagnosed with histopathology and immunohistochemistry. Our research aims to develop a minimally invasive method for diagnosing, grading and molecular typing glioma. Methods: We collected patients who underwent surgery for glioma, Trigeminal neuralgia/Hemifacial spasm, schwannoma, pituitary adenomas and meningioma at our hospital from June 2019 to June 2021. Preoperative WBCs, neutrophils, lymphocytes, monocytes, platelet counts and albumin levels were collected. Preoperative NLR, dNLR, PLR, LMR and PNI were calculated, and the correlation between them and glioma diagnosis as well as grading was analyzed. We also evaluated the diagnostic significance of NLR, dNLR, PLR, LMR, PNI and their combinations for gliomas, particularly GBM, as well as the diagnostic significance of IDH molecular typing of gliomas. Results: There were 182 healthy samples and 3101 diseased samples in our study. Compared with other groups, glioma patients had significantly higher preoperative NLR, dNLR and PLR values, but lower LMR and PNI values. Further analysis showed that NLR, dNLR, and PLR were positively correlated with glioma grading, while LMR and PNI were negatively correlated with glioma grading. For the diagnosis of glioma, NLR showed a maximum AUC value of 0.8099 (0.7823-0.8374). For GBM, NLR showed a maximum AUC value of 0.9585 (0.9467-0.9703). In the combination, NLR+dNLR showed the highest AUC value of 0.8070(0.7849-0.8291). NLR showed significant statistical significance in all grades of glioma IDH molecular typing, while PLR did not show statistical significance. Conclusions: NLR has the greatest value for the diagnosis, differential diagnosis, grading and molecular typing of gliomas. The NLR+dNLR combination also showed high sensitivity and specificity. We believe that inflammatory parameters may serve as economical and specific markers for glioma diagnosis, grading, molecular typing, and progression.
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Objective: To design a multidisciplinary enhanced recovery after surgery (ERAS) protocol for glioma patients undergoing elective craniotomy and evaluate its clinical efficacy and safety after implementation in a tertiary neurosurgical center in China. Methods: ERAS protocol for glioma patients was developed and modified based on the best available evidence. Patients undergoing elective craniotomy for treatment of glioma between September 2019 to May 2021 were enrolled in a randomized clinical trial comparing a conventional neurosurgical perioperative care (control group) to an ERAS protocol (ERAS group). The primary outcome was postoperative hospital length of stay (LOS). Secondary outcomes were 30-day readmission rate, postoperative complications, duration of the drainage tube, time to first oral fluid intake, time to ambulation and functional recovery status. Results: A total of 151 patients were enrolled (ERAS group: n = 80; control group: n = 71). Compared with the control group, postoperative LOS was significantly shorter in the ERAS group (median: 5 days vs. 7 days, p<0.0001). No 30-day readmission or reoperation occurred in either group. The time of first oral intake, urinary catheter removal within 24 h and early ambulation on postoperative day (POD) 1 were earlier and shorter in the ERAS group compared with the control group (p<0.001). No statistical difference was observed between the two groups in terms of surgical- and nonsurgical-related complications. Functional recovery in terms of Karnofsky Performance Status (KPS) scores both at discharge and 30-day follow-up was similar in the two groups. Moreover, no significant difference was found between the two groups in the Hospital Anxiety and Depression Scale (HADS) scores. Conclusion: The implementation of the ERAS protocol for glioma patients offers significant benefits over conventional neurosurgical perioperative management, as it is associated with enhancing postoperative recovery, without additional perioperative complications and risks. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=42016), identifier ChiCTR1900025108.
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Objective: To evaluate the rate of, reasons for, and predictors of unplanned reoperation after craniotomy for glioma in a single-institution consecutive series. Methods: Patients who underwent glioma resection at our hospital from 2015 to 2021 were included (n=1563). Multivariate logistic regression was used to examine the predictors of early unplanned cranial reoperation. The predictors that were screened included patient age, sex, tumor properties, blood loss, blood pressure and antiplatelets drugs usage. Results: A total of 3.6% (56/1563) of the patients underwent an early unplanned reoperation after craniotomy for glioma. The reasons for early unplanned reoperation were brain edema (48.2%), cerebral infarction (33.9%) and hemorrhage (17.9%). The predictors of early unplanned reoperation were WHO grade III-IV, peritumoral edema ≥1 cm, subtotal resection, arterial/venous involvement and elevation in blood pressure ≥50 mmHg. Conclusions: Glioma properties and blood pressure management are decisive predictors of early unplanned reoperation for glioma resection. The authors provide a nuanced discussion regarding early unplanned reoperations and perioperative process improvement as a quality indicator for glioma patient populations.
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N6-methyladenosine (m6A) RNA methylation is an emerging epigenetic modification in recent years and epigenetic regulation of the immune response has been demonstrated, but the potential role of m6A modification in GBM tumor microenvironment (TME) cell infiltration and stemness remain unknown. The m6A modification patterns of 310 GBM samples were comprehensively evaluated based on 21 m6A regulators, and we systematically correlated these modification patterns with TME cell infiltration characteristics and stemness characteristics. Construction of m6Ascore to quantify the m6A modification patterns of individual GBM samples using a principal component analysis algorithm. We identified two distinct patterns of m6A modification. The infiltration characteristics of TME cells in these two patterns were highly consistent with the immunophenotype of the GBM, including the immune activation differentiation pattern and the immune desert dedifferentiation pattern. We also identified two modes of regulation of immunity and stemness by m6A methylation. Stromal activation and lack of effective immune infiltration were observed in the high m6Ascore subtype. Pan-cancer analysis results illustrate a significant correlation between m6AScore and tumor clinical outcome, immune infiltration, and stemness. Our work reveals that m6A modifications play an important role in the development of TME and stemness diversity and complexity. Patients with a low m6AScore showed significant therapeutic advantages and clinical benefits. Assessing the m6A modification pattern of individual tumors will help enhance our knowledge of TME infiltration and stemness characteristics, contribute to the development of immunotherapeutic strategies.
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Introduction: Secondary gliosarcomas (SGS) are rare malignancies that are diagnosed subsequent to pre-existing glioma. Clinical features and optimal treatment strategies for SGS have not been conclusively established. This study aimed to assess the clinicopathological features and outcomes of SGS. Methods: We assessed the clinicopathological features and outcomes of SGS via retrospective analysis of data for SGS patients at Tangdu Hospital. Data from SGS patients in prior publications were also analyzed in accordance with PRISMA guidelines. Results: Eighteen SGS patients who had been treated at Tangdu Hospital between 2013 and 2020 were enrolled in this study. Additional 89 eligible SGS patients were identified from 39 studies. The median age for the patients was 53 years old, and the most common location was the temporal lobe. The most common initial diagnosis was glioblastoma (GBM) (72.0%). Radiology revealed enhanced masses in 94.8% (73/77) of patients. Ten patients (10/107, 9.35%) had extracranial metastases at or after SGS diagnosis. Patients with initial diagnosis of non-GBM and who were younger than 60 years of age were significantly associated with a long duration of disease progression to SGS. After SGS diagnosis, patients with initial non-GBM diagnosis, gross total resection and chemoradiotherapy exhibited prolonged survival outcomes. Patients who had been initially diagnosed with GBM and received both chemoradiotherapy and active therapy after disease progression to SGS, had a significantly longer overall survival than patients who did not. Conclusion: Initial diagnosis of GBM was a poor prognostic factor for SGS. Patients who underwent gross total resection and chemoradiation had better overall survival outcomes than those who did not. However, during treatment, clinicians should be cognizant of possible extracranial metastases.
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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.
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The spread of COVID-19 has led students to take classes online (rather than face-to-face) worldwide, including in China. For this study, we conducted qualitative focus group discussions to identify the experience of and difficulties faced by online physical education students in higher education taking online classes, including the impact on their physical activity performance, as well as some health problems they face while taking online classes during the quarantine period, such as weight gain, depression, and anxiety. Finally, utilizing Mayer's learning model as a conceptual framework, we propose a method that addresses how to effectively manage an optimal future learning system for physical education students, both during and after the COVID-19 outbreak situation. During the isolation period of COVID-19, the required equipment for the participants was rarely available at home while attending the online classes, which inevitably reduced the number of physical education units that could be conveyed. This resulted in a transfer of attention from competition to underperformance, weight gain, and adverse psychological conditions. We conclude that it is important to review and systematize the methods of online physical education learning, particularly highlighting the cultural and educational characteristics of different countries, and to investigate the effectiveness of online physical education as a whole.
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PURPOSE: Glioblastoma multiforme (GBM) is an aggressive brain tumor with a rather short survival time. Mutation of p53 has been observed and reported to play critical roles in the progression of GBM. However, the pathological mechanisms are still unclear. This study was designed to identify the role of miR-154 in mediating the biological functions of p53 in glioblastoma multiforme. METHODS: In the current study, the expression of miR-154 in GBM tissue samples and cell lines with wt-p53 or mutant p53 was evaluated. The functions of miR-154 in tumor migration, invasion and epithelial-mesenchymal transition were analyzed in vitro. A luciferase reporter assay was used to identify the target of miR-154. RESULTS: We found that expression of miR-154 was much lower in patient tissues with mutant p53. Further study revealed that p53 was a transcription factor of miR-154 and that the R273H mutation led to its inactivation. In addition, overexpression of miR-154 remarkably suppressed cell migration, invasion and EMT in vitro and tumor growth in vivo. Moreover, TCF12 was proven to be a direct target of miR-154, and the tumor suppressive effect of miR-154 was reversed by TCF12. CONCLUSION: Overall, miR-154, which was regulated by wt-p53, inhibited migration, invasion and EMT of GBM cells by targeting TCF12, indicating that miR-154 may act as a biomarker and that the p53/miR-154/TCF12 pathway could be a potential therapeutic target for GBM.
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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.
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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.
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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.