Polyurethane scaffold-based 3D lung cancer model recapitulates in vivo tumor biological behavior for nanoparticulate drug screening.

Lung cancer is the leading cause of cancer mortality worldwide. Preclinical studies in lung cancer hold the promise of screening for effective antitumor agents, but mechanistic studies and drug discovery based on 2D cell models have a high failure rate in getting to the clinic. Thus, there is an urgent need to explore more reliable and effective in vitro lung cancer models. Here, we prepared a series of three-dimensional (3D) waterborne biodegradable polyurethane (WBPU) scaffolds as substrates to establish biomimetic tumor models in vitro. These 3D WBPU scaffolds were porous and could absorb large amounts of free water, facilitating the exchange of substances (nutrients and metabolic waste) and cell growth. The scaffolds at wet state could simulate the mechanics (elastic modulus ∼1.9 kPa) and morphology (porous structures) of lung tissue and exhibit good biocompatibility. A549 lung cancer cells showed adherent growth pattern and rapidly formed 3D spheroids on WBPU scaffolds. Our results showed that the scaffold-based 3D lung cancer model promoted the expression of anti-apoptotic and epithelial-mesenchymal transition-related genes, giving it a more moderate growth and adhesion pattern compared to 2D cells. In addition, WBPU scaffold-established 3D lung cancer model revealed a closer expression of proteins to in vivo tumor, including tumor stem cell markers, cell proliferation, apoptosis, invasion and tumor resistance proteins. Based on these features, we further demonstrated that the 3D lung cancer model established by the WBPU scaffold was very similar to the in vivo tumor in terms of both resistance and tolerance to nanoparticulate drugs. Taken together, WBPU scaffold-based lung cancer model could better mimic the growth, microenvironment and drug response of tumor in vivo. This emerging 3D culture system holds promise to shorten the formulation cycle of individualized treatments and reduce the use of animals while providing valid research data for clinical trials.

Single-cell RNA sequencing highlights intratumor heterogeneity and intercellular network featured in adamantinomatous craniopharyngioma.

Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory. Little is known about cellular atlas and biological features of ACP. Here, we carried out integrative analysis of 44,038 single-cell transcriptome profiles to characterize the landscape of intratumoral heterogeneity and tumor microenvironment (TME) in ACP. Four major neoplastic cell states with distinctive expression signatures were defined, which further revealed the histopathological features and elucidated unknown cellular atlas of ACP. Pseudotime analyses suggested potential evolutionary trajectories between specific neoplastic cell states. Notably, a distinct oligodendrocyte lineage was identified in ACP, which was associated with immunological infiltration and neural damage. In addition, we described a tumor-centric regulatory network based on intercellular communication in TME. Together, our findings represent a unique resource for deciphering tumor heterogeneity of ACP, which will improve clinical diagnosis and treatment strategies.

XGBoost Machine Learning Algorithm for Prediction of Outcome in Aneurysmal Subarachnoid Hemorrhage.

Background: Patients suffered aneurysmal subarachnoid hemorrhage (aSAH) usually develop poor survival and functional outcome. Evaluating aSAH patients at high risk of poor outcome is necessary for clinicians to make suitable therapeutical strategy. This study is conducted to develop prognostic model using XGBoost (extreme gradient boosting) algorithm in aSAH. Methods: A total of 351 aSAH patients admitted to West China hospital were identified. Patients were divided into training set and test set with ratio of 7:3 to testify the predictive value of XGBoost based prognostic model. Additionally, logistic regression model was also constructed and compared with XGBoost based model. Area under the receiver operating characteristic curve (AUC), sensitivity and specificity were calculated to evaluate the value of XGBoost and logistic regression. Results: There were 74 (21.1%) non-survivors and 148 (42.1%) patients with unfavorable functional outcome. Non-survivors had older age (p=0.025), lower Glasgow coma scale (GCS) (p<0.001), higher World Federation of Neurosurgical Societies WFNS score (p<0.001), mFisher score (p<0.001). The incidence of intraventricular hemorrhage (IVH) (p=0.025) and delayed cerebral ischemia (DCI) (p<0.001) was higher in non-survivors than survivors. The AUC of XGBoost model for predicting mortality and unfavorable functional outcome were 0.950 and 0.958, which were higher than 0.767 and 0.829 of logistic regression model. Conclusion: XGBoost based model is more precise than logistic regression model in predicting outcome of aSAH patients. Using XGBoost prognostic model is helpful for clinicians to identify high-risk aSAH patients and therefore strengthen medical care.

Surgical outcomes of spinal cavernous malformations: A retrospective study of 98 patients.

Objective: Spinal cord cavernous malformation (SCCM) is a rare vascular lesion, and the treatment strategy remains controversial at present. The goal of this retrospective study was to analyze the surgical outcomes of the SCCM and to find more appropriate treatment strategies for a better prognosis. Method: A retrospective review of 98 patients with SCCM from 2009 to 2018 was conducted at the neurosurgical center of our hospital. Neurological function was assessed using the American Spinal Injury Association (ASIA) impairment scale. Clinical features were analyzed using the multivariable logistic regression. Results: Ninety-eight patients with SCCM were included, of whom 36% were female and 64% male. The mean age was 41.6 years; and family history was reported in 8% of patients. Definite hemorrhage was found in 6%. Before surgery, the neurological status was Grade A in 2%, Grade B in 2%, Grade C in 12%, Grade D in 54%, and Grade E in 30% of the patients. 83% (81/98) patients had long-term follow-up, of whom, 42% had improved, 51% were stable and 7% had deteriorated. Patients with dorsal or superficial lesions showed better improvement than those with ventral or lateral deep lesions. Those with symptoms lasting less than three months had higher rates of improvement than those with symptoms lasting more than three months. However, there was no significant difference in prognosis between hemilaminectomy and laminectomy. Conclusion: These results suggest that surgical strategies should be preferred for severe symptomatic SCCMs if total resection can be achieved, thereby avoiding the risk of severe complications with subsequent lesion hemorrhage. Earlier (usually within 3 months of symptom duration) surgical resection generally may lead to a better prognosis. For ventral or lateral deep SCCMs, the surgical strategy should be considered more carefully.

Elevated level of D-dimer increases the risk of stroke.

The aim of this study was to systematically evaluate the association between D-dimer level and the risk of stroke through performing a meta-analysis. PubMed, Web of Science, EMBASE and Cochrane Library were searched for potentially eligible literature. Prospective observational studies or case-control studies were included. The study characteristics and relevant data were extracted. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to estimate the association between D-dimer level and the risk of stroke. Seven prospective studies with 22,207 patients and three case-control studies with 2,248 patients were included. For the prospective studies, the pooled HRs of higher D-dimer level for all types of stroke, ischemic stroke and hemorrhagic stroke were 1.55 (95% CI, 1.28- 1.87), 1.62 (95% CI, 1.18-2.22) and 1.30 (95% CI, 0.63-2.68), respectively. The pooled HRs per SD increase in log D-dimer for all types of stroke, ischemic stroke and hemorrhagic stroke were 1.16 (95% CI, 1.06-1.26), 1.11 (95% CI, 1.03-1.21) and 1.11 (95% CI, 0.95-1.30), respectively. For the case-control studies, the pooled OR of higher D-dimer level for acute ischemic stroke was 2.06 (95% CI, 1.08-3.96). No significant publication bias was found in the meta-analysis. In conclusion, our results suggested that higher D-dimer level was associated with higher risk of stroke, especially ischemic stroke.

World Health Organization Grade II Meningiomas: The Role of Adjuvant/Salvage Gamma Knife Surgery After Initial Surgery and Prognostic Factor Assessment.

OBJECTIVE: This study was performed to evaluate the efficiency of Gamma Knife surgery (GKS) on reducing recurrence of World Health Organization (WHO) grade II meningiomas after surgery and to define the risk factors associated with tumor recurrence/progression and patient's death. METHODS: This retrospective study included 75 patients who were diagnosed with WHO grade II meningiomas after initial surgery. The Kaplan-Meier method with a log-rank test was used to calculate the survival curves. Univariate and multivariate Cox proportional hazards model were used to identify the risk factors associated with tumor recurrence/progression and patient's death. RESULTS: The median follow-up period was 70 months. The overall survival (OS) was 97.2% at 2 years and 89.8% at 5 years. The progression-free survival (PFS) at 1, 3, and 5 years was 89.3%, 72.6%, and 59.3%, respectively. Comparing the effects on PFS and OS between different groups, there were no statistically significant differences between the surgery-alone group and the surgery with adjuvant/salvage GKS group (P = 0.512; P = 0.949). In multivariate Cox proportional hazards model analysis, extent of resection (P = 0.001) and tumor location (P = 0.015) were associated with tumor recurrence; only histologic subtypes (P = 0.005) were associated with patient's death. CONCLUSIONS: There was no significant PFS or OS benefit for patients with WHO grade II meningiomas treated with adjuvant/salvage GKS postoperatively. Convexity meningiomas with gross total resection tended to benefit PFS. We suggest trying to achieve maximum safe gross total resection for patients with WHO grade II meningiomas, then following up closely.

Prognostic role of neutrophil lymphocyte ratio in patients with spontaneous intracerebral hemorrhage.

The aim of this study was to evaluate the prognostic role of neutrophil lymphocyte ratio (NLR) in patients with spontaneous intracerebral hemorrhage (ICH). PubMed, EMBASE, Web of Knowledge, Cochrane Library and China National Knowledge Infrastructure were searched for potentially relevant literature. The study and patient characteristics were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to estimate the prognostic role of NLR in patients with ICH. Poor functional outcome was defined as modified Rankin Scale≥3. Four studies with 1,720 patients were included. The pooled OR of higher NLR for poor functional outcome at 3 months was 2.74 (95% CI, 1.33-5.65). The pooled OR of higher NLR for death at 3 months was 1.58 (95% CI, 0.44-5.68). Subgroup analysis and sensitivity analysis were also performed. Publication bias was not present. In conclusion, for patients with ICH, higher NLR was associated with poorer functional outcome at 3 months, while higher NLR was not associated with higher risk of death at 3 months.

Predictive value of preoperative retinal nerve fiber layer thickness for postoperative visual recovery in patients with chiasmal compression.

The aim of this study was to evaluate the predictive role of preoperative retinal nerve fiber layer (RNFL) thickness for postoperative visual recovery in patients with chiasmal compression through performing a meta-analysis. PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure were searched for relevant studies. The study and patient characteristics were extracted. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to estimate the predictive value of RNFL thickness. Subgroup analyses were also performed. Four studies with 202 patients and 395 eyes were included. The pooled results showed that patients with normal RNFL thickness could achieve better visual recovery compared with those with thin RNFL with the OR of 15.61 (95% CI, 4.09-59.61). Significant heterogeneity was observed (I2 = 54.5%, P=0.086). Publication bias was not present. Normal preoperative RNFL thickness could predict better postoperative visual recovery than thin RNFL in patients with chiasmal compression.

Prognostic factors for patients with World Health Organization grade III meningiomas treated at a single center.

We analyzed the characteristics of patients with World Health Organization (WHO) grade III meningioma to identify factors that may predict tumor recurrence and overall survival (OS).We retrospectively reviewed the patients diagnosed with WHO grade III meningioma who were surgically treated at our institute between 2008 and 2016. Survival outcome was assessed by Kaplan-Meier analysis. Cox regression analyses were performed to identify the prognostic factors associated with tumor recurrence and OS.Forty-two patients were included. The mean follow-up time was 23.2 months (range 2-75 months). At the end of analysis, 30 patients were found with tumor recurrence. The 1-year, 3-year, and 5-year recurrence-free survival (RFS) were 51.6%, 33.9%, and 12.0%, respectively. At final follow-up, 23 patients were deceased, the 1-year, 3-year, and 5-year OS were 66.2%, 39.7%, and 35.8%, respectively. Twenty-eight newly diagnosed patients were included, and the 1-year, 3-year, and 5-year RFS were 63.5%, 44.3%, and 19.4%, respectively, and the 1-year, 3-year, and 5-year OS were 74.6%, 52.5%, and 46.7%, respectively. Extent of resection was the only factor associated with tumor recurrence and OS.WHO grade III meningioma is rare, and difficult to manage with a high rate of recurrence and poor OS. Extent of resection is an independent prognostic factor related to tumor recurrence and OS. We could not confirm the usefulness of Ki-67. We suggest that more aggressive treatment, such as safety maximizing cytoreduction by surgery, would improve treatment outcomes.