Efficacy of Outside-In Hip Arthroscopy without Traction in the Treatment of Hip Synovial Osteochondromatosis.

Arthroscopic treatments of hip synovial osteochondromatosis are mostly performed under traction, resulting in neurovascular injury or iatrogenic damage to the labrum or cartilage. This study aimed to assess the effectiveness of outside-in hip arthroscopy without traction in treating hip synovial osteochondromatosis. This retrospective study was conducted on a series of patients with hip synovial osteochondromatosis treated using outside-in hip arthroscopy without traction in our hospital between 2018 and 2020. Plain radiography and magnetic resonance imaging (MRI) scans were obtained. The Harris hip score (HHS), hip range of motion (ROM), and visual analog scale (VAS) scores were analyzed. The preoperative scores and last follow-up scores were compared with a paired-sample t test. The complications and recurrence postsurgery were recorded. This study included five patients (three male and two female) with an average age of 41 years (range 28-54 years). The mean follow-up time was 25.2 months (range 18-36 months). All patients experienced groin pain relief and improved ROM. The mean VAS score was significantly lower postoperatively (0.4 ± 0.5) than preoperatively (3.2 ± 0.8) (p < 0.001). The mean HHS improved from 58.6 ± 12.7 (range 43-73) to 89.8 ± 5.26 (range 81-95) (p < 0.001). No major complications, including infection, perineal numbness and swelling, neurotrosis, thromboembolism, or severe persistent pain, were reported. Synovial osteochondromatosis recurred in one patient after 2 years of follow-up without any obvious symptoms such as hip pain or joint locking. Therefore, no further treatment was necessary. This study showed that outside-in hip arthroscopy without traction might be a viable option for treating hip synovial osteochondromatosis, effectively and safely relieving symptoms with minimal complications, especially in patients without lesions in the central compartment.

Estimates of natural frequencies for nuclear vibration, and an assessment of the feasibility of selective ultrasound ablation of cancer cells.

Selective ablation of cancer cells by ultrasound would be transformative for cancer therapy, but has not yet been possible. A key challenge is that cancerous and non-cancerous cells typically have similar acoustic impedance and are thus indistinguishable as materials in their responses to ultrasound. However, in certain cancers, cytoskeletal and nuclear lamin structures differ between healthy and malignant cells, opening the possibility of exploiting structural differences that manifest as different vibrational responses. To assess the possibility that the nuclei of certain cancerous cells might vibrate at different frequencies, we measured sizes and effective indentation moduli of a range of cancerous and non-cancerous cells from several cell lines and regions of the brain, and estimated the natural frequencies for nuclear vibration. Results suggest a potential difference in natural frequency for nuclear vibration between certain cancerous and non-cancerous cells, on the order of tens of kHz. This gap is potentially sufficient for selective ablation and motivates future experimentation on these specific cell types.

Safety and Efficiency of Anlotinib in Patients with Recurrent Grade 4 Glioma: A Single-Center Retrospective Analysis.

PURPOSE: Anlotinib is a multi-target TKI which has been used in different advanced tumors. However, its efficiency and safety in patients with glioblastoma are still not well discussed. This retrospective study aimed to discover the safety and efficiency of anlotinib in recurrent grade 4 glioma. METHODS: The clinical data of patients with recurrent grade 4 glioma treated with anlotinib in our center were collected and analyzed. The progression-free survival (PFS), overall survival (OS), and OS after recurrence were calculated by Kaplan-Meier method and compared by log-rank test. Sub-group analysis was used to find possible variables that affect survival. RESULTS: From October 2017 to December 2020, seventeen patients with recurrent grade 4 glioma treated with anlotinib were enrolled. The median age was 50 with 13 males. The median KPS was 70. All patients received standard STUPP mode treatment before recurrence. The median PFS was 7 months [95% confidence interval (CI) 5.3-8.6]. The median OS after first diagnosis was 17 months (95% CI 15.7-18.3). The median OS after recurrence was 10 months (95% CI 7.6-12.4). The objective response rate was 33.33% (5/15), and the disease control rate was 60% (9/15). The existence of target genes was identified as a variable affecting the survival after recurrence. The median OS after recurrence in patients with target genes was 12 months (95% CI 6.9-17.1), whereas for patients without targets, the median OS was 4 months (95% CI 1.9-6.1) and for patients with an unknown status, the median OS was 10 months (95% CI 8.4-11.6) (P = 0.013). CONCLUSION: For recurrent grade 4 glioma, anlotinib can be considered as a supplement to the standard STUPP treatment, especially for the patient with anlotinib target genes.

Endocrine Outcomes and Associated Predictive Factors for Somatotrophin Pituitary Adenoma after Endoscopic Endonasal Transsphenoidal Surgery: 10 Years of Experience in a Single Institute.

Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level ( p = 0.166), basal GH level ( p = 0.001), and nadir GH level ( p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891-0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.

GNAS mutations suppress cell invasion by activating MEG3 in growth hormone-secreting pituitary adenoma.

Approximately 30%-40% of growth hormone-secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in GNAS (α subunit of stimulatory G protein). Mutations in GNAS are associated with clinical features of smaller and less invasive tumors. However, the role of GNAS mutations in the invasiveness of GHPAs is unclear. GNAS mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 (MEG3) was evaluated with RT-qPCR. MEG3 was manipulated in GH3 cells using a lentiviral expression system. Cell invasion ability was measured using a Transwell assay, and epithelial-mesenchymal transition (EMT)-associated proteins were quantified by immunofluorescence and western blotting. Finally, a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type GNAS. Consistently, the invasiveness of mutant GNAS-expressing GH3 cells decreased. MEG3 is uniquely expressed at high levels in GHPAs harboring mutated GNAS. Accordingly, MEG3 upregulation inhibited tumor cell invasion, and conversely, MEG3 downregulation increased tumor cell invasion. Mechanistically, GNAS mutations inhibit EMT in GHPAs. MEG3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/ß-catenin signaling pathway, which was further validated in vivo. Our data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/ß-catenin signaling pathway.

Fully endoscopic approach for resection of brainstem cavernous malformations: a systematic review of the literature.

BACKGROUND: Brainstem cavernous malformations (BCMs) are benign lesions that typically have an acute onset and are associated with a high rate of morbidity. The selection of the optimal surgical approach is crucial for obtaining favorable outcomes, considering the different anatomical locations of various brainstem lesions. Endoscopic surgery is increasingly utilized in treating of BCMs, owing to its depth illumination and panoramic view capabilities. For intra-axial ventral BCMs, the best surgical options are endoscopic endonasal approaches, following the "two-point method. For cavernous hemangiomas on the dorsal side of the brainstem, endoscopy proves valuable by providing enhanced visualization of the operative field and minimizing the need for brain retraction. METHODS: In this review, we gathered data on the fully endoscopic approach for the resection of BCMs, and outlined technical notes and tips. Total of 15 articles were included in this review. The endoscopic endonasal approach was utilized in 19 patients, and the endoscopic transcranial approach was performed in 3 patients. RESULTS: The overall resection rate was 81.8% (18/22). Among the 19 cases of endoscopic endonasal surgery, postoperative cerebrospinal fluid (CSF) leakage occurred in 5 cases, with lesions exceeding 2 cm in diameter in 3 patients with postoperative CSF rhinorrhea. Among the 20 patients with follow-up data, 2 showed no significant improvement after surgery, whereas the remaining 18 patients showed significant improvement compared to their admission symptoms. CONCLUSIONS: This systematic literature review demonstrates that a fully endoscopic approach is a safe and effective option for the resection of BCMs. Further, it can be considered an alternative to conventional craniotomy, particularly when managed by a neurosurgical team with extensive experience in endoscopic surgery, addressing these challenging lesions.

Combined simultaneous transsphenoidal and transcranial regimen improves surgical outcomes in complex giant pituitary adenomas: a longitudinal retrospective cohort study.

BACKGROUND: Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. PATIENTS AND METHODS: This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. RESULTS: Out of 647 patients [298 (46.1%) women, mean age: 48.5 ± 14.0 years] with complex GPAs, 91 were in the combined group and 556 were in the noncombined group. Compared with the noncombined regimen, the combined regimen was associated with a higher probability of gross total resection [50.5% vs. 40.6%, odds ratio (OR): 2.18, 95% confidence interval (CI): 1.30-3.63, P = 0.003]. The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h ( P < 0.001) and higher surgical costs of 22,000 CNY (~ 3,000 USD, P = 0.022) compared with the noncombined approach. CONCLUSIONS: The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.

Comparison of the Endoscopic Endonasal Approach with the Endoscopic Supraorbital Keyhole Approach to the Tuberculum Sellae Region: A Quantitatively Cadaveric Study.

BACKGROUND: The endoscopic endonasal approach (EEA) and the endoscopic supraorbital keyhole approach (eSKA) provide minimally invasive access to tuberculum sellae (TS) tumors. Evaluation of the operating maneuverability is helpful for approach selection. Herein, we compared the two approaches and aimed to provide quantitative anatomic data for surgical decision-making in the management of TS lesions. METHODS: Fifteen dissections were performed on five silicone-injected cadaveric heads. The EEA and eSKA (both right and left) were performed on each head. Surgical freedom and working angles in the axial and sagittal planes were calculated using the stereotactic navigation system in the selected six targets: the midpoint of the leading edge of the sphenoid sinus (leSS), the midpoint of the edge of the dorsum sellae (eDS), the ipsilateral medial opticocarotid recess (imOCR), the contralateral medial opticocarotid recess (cmOCR), the ipsilateral lateral opticocarotid recess (ilOCR), and the contralateral lateral opticocarotid recess (clOCR). RESULTS: The surgical freedom at the ilOCR and the axial working angles at the leSS, ilOCR, and imOCR (imOCR with excessive manipulation of the optic apparatus) were greater in the eSKA. The EEA provided greater surgical freedom and/or working angles at most targets than eSKA (the surgical freedom at the imOCR, cmOCR, clOCR, and eDS; the axial working angles at the cmOCR and clOCR; and the sagittal working angles at the leSS, imOCR, cmOCR, clOCR, and eDS). CONCLUSION: The EEA provides greater surgical freedom and working angles for paramedian lesions, whereas the eSKA provides better surgical maneuverability for lesions with lateral extension.

DE-UFormer: U-shaped dual encoder architectures for brain tumor segmentation.

Objective. In brain tumor segmentation tasks, the convolutional neural network (CNN) or transformer is usually acted as the encoder since the encoder is necessary to be used. On one hand, the convolution operation of CNN has advantages of extracting local information although its performance of obtaining global expressions is bad. On the other hand, the attention mechanism of the transformer is good at establishing remote dependencies while it is lacking in the ability to extract high-precision local information. Either high precision local information or global contextual information is crucial in brain tumor segmentation tasks. The aim of this paper is to propose a brain tumor segmentation model that can simultaneously extract and fuse high-precision local and global contextual information.Approach. We propose a network model DE-Uformer with dual encoders to obtain local features and global representations using both CNN encoder and Transformer encoder. On the basis of this, we further propose the nested encoder-aware feature fusion (NEaFF) module for effective deep fusion of the information under each dimension. It may establishe remote dependencies of features under a single encoder via the spatial attention Transformer. Meanwhile ,it also investigates how features extracted from two encoders are related with the cross-encoder attention transformer.Main results. The proposed algorithm segmentation have been performed on BraTS2020 dataset and private meningioma dataset. Results show that it is significantly better than current state-of-the-art brain tumor segmentation methods.Significance. The method proposed in this paper greatly improves the accuracy of brain tumor segmentation. This advancement helps healthcare professionals perform a more comprehensive analysis and assessment of brain tumors, thereby improving diagnostic accuracy and reliability. This fully automated brain model segmentation model with high accuracy is of great significance for critical decisions made by physicians in selecting treatment strategies and preoperative planning.

A Preoperative Nomogram for Prediction of Postoperative Hypocortisolism in Patients with Pituitary Adenomas: A Single-Center Retrospective Cohort Study.

BACKGROUND: Patients with pituitary adenomas (PAs) are at an increased risk preoperatively and postoperatively for hypopituitarism. Postoperative hypocortisolism is associated with increased mortality and morbidity as well as poor quality of life. However, research about the risk factors for postoperative hypocortisolism is limited, and a predictive nomogram for postoperative hypocortisolism has not yet been developed. We aimed to investigate the predictive factors for postoperative hypocortisolism and construct a dynamic online nomogram. METHODS: Our database included 438 consecutive PA patients who were hospitalized and treated with transsphenoidal surgery by experienced neurosurgeons from the different medical teams in the Neurosurgery Department, Jinling Hospital, between January 2018 and October 2020. The final study group included 238 eligible patients. Data on possible predictors, including age, sex, treatment history of PAs, preoperative signs and symptoms, primary recurrence subtype, and clinical subtypes, were collected. Univariable and multivariable logistic regression analyses were applied to identify independent predictors, which were included in constructing the nomogram model. The calibration curve and receiver operating characteristic curve were computed to evaluate the predictive performance of the nomogram model. RESULTS: The incidence of postoperative hypocortisolism was 12.08%. Three preoperative predictors were identified to construct the nomogram: surgical type (microscopic or endoscopic, with endoscopic surgery proven to be the protective factor) (odds ratio, 0.24; 95% confidence interval [CI], 0.093-0.610; P = 0.003), prothrombin time (odds ratio, 2.40; 95% CI, 1.332-4.326; P = 0.004), and basophil cell count (odds ratio, 5.25; 95% CI, 1.270-21.816; P = 0.022,). The area under the curve of receiver operating characteristic curve for the constructed nomogram was 0.749 (95% CI, 0.640-0.763); a well-fixed calibration curve was generated for the nomogram model. An interactive web-based dynamic nomogram application was also constructed. CONCLUSIONS: In this study, surgical type, prothrombin time, and basophil cell count were the most relevant predictive factors for postoperative hypocortisolism. A predictive nomogram that can preoperatively assess the risk of hypocortisolism after surgical treatment of PAs was developed. This nomogram could be helpful in identifying high-risk patients who require close monitoring of serum cortisol levels and initiating clinical procedures for patients requiring cortisol administration therapy as a lifesaving strategy.

Comprehensive analysis of m6A subtype classification for immune microenvironment of pituitary adenomas.

BACKGROUND: N6-methyladenosine (m6A) RNA methylation and tumor immune microenvironment (IME) have an essential role in tumor development. However, their relationships in pituitary adenomas (PAs) remains unclear. METHODS: PA datasets from the Gene Expression Omnibus (GEO) and European Bioinformatics Institute (EMBL-EBI) were used. We utilized hierarchical clustering algorithms based on the m6A regulator gene set to identify m6A subtypes. ESTIMATE and CIBERSORT algorithms were applied to explore the compositions of stromal and immune cells. A nomogram model was constructed for the prediction of m6A subtypes in PAs. Immunohistochemistry and multiplex immunofluorescence staining were used to analyze the expression level of m6A regulator YTHDF2 in relation to M2 macrophages and immune checkpoints in PAs. RESULTS: We concluded the IME landscape of m6A subtype classification and characterized two emerging m6A subtypes. Different IME between these two m6A subtypes were identified. Simultaneously, a polygenic nomogram model was constructed for predicting m6A subtype classification, with excellent predictive performance (training set, AUC = 0.984; validation set, AUC = 0.986). YTHDF2 was highly expressed in PAs and accompanied by upregulated M2 macrophages and expression of PD-L1. CONCLUSIONS: We proposed two novel m6A subtypes in PAs for the first time and constructed a reliable and clinically accessible nomogram model for them. Meanwhile, YTHDF2 was first identified as a promising biomarker for immunotherapy and potential molecular target in PAs.

Predictors and dynamic online nomogram for postoperative delayed hyponatremia after endoscopic transsphenoidal surgery for pituitary adenomas: a single-center, retrospective, observational cohort study with external validation.

BACKGROUND: Postoperative delayed hyponatremia (PDH) is a major cause of readmission after endoscopic transsphenoidal surgery (eTSS) for pituitary adenomas (PAs). However, the risk factors associated with PDH have not been well established, and the development of a dynamic online nomogram for predicting PDH is yet to be realized. We aimed to investigate the predictive factors for PDH and construct a dynamic online nomogram to aid in its prediction. METHODS: We analyzed the data of 226 consecutive patients who underwent eTSS for PAs at the Department of Neurosurgery in Jinling Hospital between January 2018 and October 2020. An additional 97 external patients were included for external validation. PDH was defined as a serum sodium level below 137 mmol/L, occurring on the third postoperative day (POD) or later. RESULTS: Hyponatremia on POD 1-2 (OR = 2.64, P = 0.033), prothrombin time (PT) (OR = 1.78, P = 0.008), and percentage of monocytes (OR = 1.22, P = 0.047) were identified as predictive factors for PDH via multivariable logistic regression analysis. Based on these predictors, a nomogram was constructed with great discrimination in internal validation (adjusted AUC: 0.613-0.688) and external validation (AUC: 0.594-0.617). Furthermore, the nomogram demonstrated good performance in calibration plot, Brier Score, and decision curve analysis. Subgroup analysis revealed robust predictive performance in patients with various clinical subtypes and mild to moderate PDH. CONCLUSIONS: Preoperative PT and the percentage of monocytes were, for the first time, identified as predictive factors for PDH. The dynamic nomogram proved to be a valuable tool for predicting PDH after eTSS for PAs and demonstrated good generalizability. Patients could benefit from early identification of PDH and optimized treatment decisions.

National Brain Tumour Registry of China (NBTRC) statistical report of primary brain tumours diagnosed in China in years 2019-2020.

Background: The lack of a well-designed brain tumour registry with standardized pathological diagnoses in underdeveloped countries hinders the ability to compare epidemiologic data across the globe. The National Brain Tumour Registry of China (NBTRC), created in January 2018, is the first multi-hospital-based brain tumour registry in China. Patient data reported to the NBTRC in years 2019-2020 were assessed. Methods: Tumour pathology was based on the 2016 World Health Organization (WHO) classification of tumours of the central nervous system and ICD-O-3. The anatomical site was coded per the Surveillance, Epidemiology, and End Results (SEER) solid tumour module (version of July 2019). The cases were tabulated by histology and anatomical site. Categorical variables were reported as numbers (percentages). The distribution of tumours by age (0-14, 15-19, 20-39, 40-64, and 65+ years) was analysed. Findings: There were a total of 25,537 brain tumours, foremost among them meningioma (23.63%), followed by tumours of the pituitary (23.42%), and nerve sheath tumours (9.09%). Glioblastoma, the most common and lethal form of primary brain cancer in adults, represented 8.56% of all cases. Of note, 6.48% of the malignant tumours were located in the brain stem. The percentage of malignant brain tumours decreased with increasing age, 24.08% in adults (40+ years), 30.25% in young adults (20-39 years), 35.27% in adolescents (15-19 years), and 49.83% in children (0-14 years). Among the 2107 paediatric patients, the most common sites were ventricle (17.19%), brainstem (14.03%), pituitary and craniopharyngeal duct (13.4%), and cerebellum (12.3%), a distribution that differed from that of the entire cohort. The histology distribution was also unique in children, with glioblastoma much less incident compared to the whole cohort (3% vs. 8.47%, p < 0.01). 58.80% of all patients chose higher-level neurosurgical hospitals outside of their province of residence. The median in-hospital length of stay (LOS) for the various pathologies ranged from 11 to 19 days. Interpretation: The histological and anatomical site distribution of brain tumours in the NBTRC was statistically different in the subgroup of children (0-14 years). Patient choice of pursuing trans-provincial treatment was common and the in-hospital LOS was longer compared to that reported in similar European and American patient populations, which merits further attention. Funding: The National Key Research and Development Program of China (2015BAI12B04, 2013BAI09B03, 2014BAI04B01, and 2021YFF1201104) and Chinese National Natural Science Foundation of China (81971668).

Endoscopic endonasal transsphenoidal surgery for the cavernous sinus hemangioma: Surgical application and review of the literature.

Aim: Cavernous sinus hemangiomas (CSHs) are hypervascular malformations and the surgical treatment is technically demanding. Although some articles have reported resection of CSHs using endoscopic endonasal transsphenoidal surgery (EETS), most of them were encountered for a lack of preoperative strategy guidance. Herein, we reported gross total resection (GTR) of intrasellar CSHs in two patients undergoing strategical EETS and compared EETS with frontotemporal craniotomy (FC) and stereotactic radiosurgery by literature review. Material and methods: Two patients with CSHs who underwent EETS were reported. The literature review was conducted to exhaust studies that reported surgical treatment for CSHs. The tumor resection rate, and the postoperative short-term and long-term newly-developed or deteriorative cranial-nerve function rates were extracted. Results: GTR was achieved with no postoperative complications in the two cases. Nine articles reported 14 cases undergoing EETS for CSHs and twenty-three articles reported 195 cases undergoing FC for CSHs. The GTR rates of EETS and FC were 57.14% (8/14) and 78.97% (154/195) respectively. The postoperative short-term and long-term newly-developed or deteriorative cranial-nerve function rates were 0% (0/7) and 0% (0/6) for the EETS group, and 57% (57/100) and 18.18% (18/99) for the FC group. According to the previous meta-analysis, stereotactic radiosurgery resulted in remarkable tumor shrinkage in 67.80% (40/59) of patients and partial shrinkage in 25.42% of patients. Discussion: The results showed that the intrasellar type of CSHs could be removed safely by EETS without crossing the nerves in the CS.

Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon-bone healing.

Tendon-bone insertion (TBI) injuries, such as anterior cruciate ligament injury and rotator cuff injury, are the most common soft tissue injuries. In most situations, surgical tendon/ligament reconstruction is necessary for treating such injuries. However, a significant number of cases failed because healing of the enthesis occurs through scar tissue formation rather than the regeneration of transitional tissue. In recent years, the therapeutic potential of mesenchymal stem cells (MSCs) has been well documented in animal and clinical studies, such as chronic paraplegia, non-ischemic heart failure, and osteoarthritis of the knee. MSCs are multipotent stem cells, which have self-renewability and the ability to differentiate into a wide variety of cells such as chondrocytes, osteoblasts, and adipocytes. Numerous studies have suggested that MSCs could promote angiogenesis and cell proliferation, reduce inflammation, and produce a large number of bioactive molecules involved in the repair. These effects are likely mediated by the paracrine mechanisms of MSCs, particularly through the release of exosomes. Exosomes, nano-sized extracellular vesicles (EVs) with a lipid bilayer and a membrane structure, are naturally released by various cell types. They play an essential role in intercellular communication by transferring bioactive lipids, proteins, and nucleic acids, such as mRNAs and miRNAs, between cells to influence the physiological and pathological processes of recipient cells. Exosomes have been shown to facilitate tissue repair and regeneration. Herein, we discuss the prospective applications of MSC-derived exosomes in TBI injuries. We also review the roles of MSC-EVs and the underlying mechanisms of their effects on promoting tendon-bone healing. At last, we discuss the present challenges and future research directions.

One-and-a-half nostril versus binostril endoscopic transsphenoidal approach to the pituitary adenomas: A prospective randomized controlled trial.

Background: Binostril endoscopic transsphenoidal approach (BETA) is the most used approach for sellar lesions nowadays, while its damage to the nasal structures may cause nasal discomfort and affect nasal functions including respiration and olfaction. With the purpose to improve the post-operative sinonasal quality of life (QoL), we introduced the one-and-a-half nostril endoscopic transsphenoidal approach (OETA) in 2016 which preserved more natural structures and registered a prospective randomized controlled trial (ChiCTR-IOR-16008222) to compare the two approaches regarding the surgical outcomes and complications. Methods: Sixty patients with pituitary adenomas were recruited and randomly assigned to the OETA group and the BETA group between April 2016 and May 2017 in Jinling Hospital. The tumor resection rate, endocrinal and visual outcomes, and surgical complications between the OETA and BETA groups were analyzed. Besides, the questionnaire Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12) was used to evaluate patients' sinonasal QoL at seven time points (pre-operative; 2-weeks, 1-month, 3-months, 6-months, 12-months, and long-term post-operatively). The Sniffin' Sticks were used to assess patients' olfactory function objectively in a long term. Each patient was followed for at least 12 months post-operatively. Results: There was no significant difference in tumor resection rate, hormonal and visual outcomes, and surgical complications between the two groups. Regarding the ASK Nasal-12, patients in the OETA group complained less about dried nasal material at 2 weeks after surgery (P = 0.017). One month after surgery, the OETA group had better olfaction function (P = 0.019) compared with the BETA group. However, there was no significant difference in early and long-term postoperative sinonasal QoL between the two approaches according to the entire ASK Nasal-12 metric. The results of the Sniffin' Sticks showed that the two groups had a similar olfactory performance at long-time follow-up. Conclusion: In this single tertiary center trial, the results showed that the OETA achieved the same surgical outcomes and post-operative sinonasal QoL as the BETA. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=13852, identifier: ChiCTR-IOR-16008222.

N6-methyladenosine-related microRNAs risk model trumps the isocitrate dehydrogenase mutation status as a predictive biomarker for the prognosis and immunotherapy in lower grade gliomas.

Aim: Lower grade gliomas [LGGs; World Health Organization (WHO) grades 2 and 3], owing to the heterogeneity of their clinical behavior, present a therapeutic challenge to neurosurgeons. The aim of this study was to explore the N6-methyladenosine (m6A) modification landscape in the LGGs and to develop an m6A-related microRNA (miRNA) risk model to provide new perspectives for the treatment and prognostic assessment of LGGs. Methods: Messenger RNA (mRNA) and miRNA expression data of LGGs were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. An m6A-related miRNA risk model was constructed via least absolute shrinkage and selection operator (LASSO), univariate, and multivariate Cox regression analysis. Next, Kaplan-Meier analysis, principal-component analysis (PCA), functional enrichment analysis, immune infiltrate analysis, dynamic nomogram, and drug sensitivity prediction were used to evaluate this risk model. Results: Firstly, six m6A-related miRNAs with independent prognostic value were selected based on clinical information and used to construct a risk model. Subsequently, compared with low-risk group, LGGs in the high-risk group had a higher m6A writer and reader scores, but a lower eraser score. Moreover, LGGs in the high-risk group had a significantly worse clinical prognosis than those in the low-risk group. Simultaneously, this risk model outperformed other clinicopathological variables in the prognosis prediction of LGGs. Immune infiltrate analysis revealed that the proportion of M2 macrophages, regulatory T (Treg) cells, and the expression levels of exhausted immune response markers were significantly higher in the high-risk group than in the low-risk group. Finally, this study constructed an easy-to-use and free dynamic nomogram to help clinicians use this risk model to aid in diagnosis and prognosis assessment. Conclusions: This study developed a m6A-related risk model and uncovered two different m6A modification landscapes in LGGs. Moreover, this risk model may provide guidance and help in clinical prognosis assessment and immunotherapy response prediction for LGGs.

BTB domain and CNC homolog 1 promotes glioma invasion mainly through regulating extracellular matrix and increases ferroptosis sensitivity.

BTB Domain and CNC Homolog 1 (Bach1) has been implicated in cancer progression, particularly in invasion, but little is unknown about its effect on glioma. Here, we confirmed that highly expressed Bach1 prominently promoted glioma invasion. Similar to the reported mechanisms in other tumors, Bach1 upregulation was also correlated with epithelial mesenchymal transition (EMT) in glioma cells. More importantly, proteomic analysis indicated that the main mechanism of Bach1 promoting invasion in glioma involved extracellular matrix (ECM). We further found thatBach1 upregulation was associated with the multiple mechanisms of ECM remodeling in glioma, including increasing the expression and deposition of ECM components, activating TGFBR2-smad2/3 signaling, promoting invadopodia formation and inducing the expression and secretion of MMP2. Meanwhile, Bach1 overexpression increased ferroptosis sensitivity in glioma cells. The ferroptosis inducer (sulfasalazine) obviously suppressed the gliomas with Bach1 upregulation in vitro and in vivo. Overall, Bach1 has a two-faced role in glioma. Highly expressed Bach1 promotes glioma invasion. Conversely, Bach1 upregulation is also a potential indicator of the sensitivity of ferroptosis inducers.

Roles of the m6A Modification of RNA in the Glioblastoma Microenvironment as Revealed by Single-Cell Analyses.

Purpose: Glioblastoma multiforme (GBM) is a common and aggressive form of brain tumor. The N6-methyladenosine (m6A) mRNA modification plays multiple roles in many biological processes and disease states. However, the relationship between m6A modifications and the tumor microenvironment in GBM remains unclear, especially at the single-cell level. Experimental Design: Single-cell and bulk RNA-sequencing data were acquired from the GEO and TCGA databases, respectively. We used bioinformatics and statistical tools to analyze associations between m6A regulators and multiple factors. Results: HNRNPA2B1 and HNRNPC were extensively expressed in the GBM microenvironment. m6A regulators promoted the stemness state in GBM cancer cells. Immune-related BP terms were enriched in modules of m6A-related genes. Cell communication analysis identified genes in the GALECTIN signaling network in GBM samples, and expression of these genes (LGALS9, CD44, CD45, and HAVCR2) correlated with that of m6A regulators. Validation experiments revealed that MDK in MK signaling network promoted migration and immunosuppressive polarization of macrophage. Expression of m6A regulators correlated with ICPs in GBM cancer cells, M2 macrophages and T/NK cells. Bulk RNA-seq analysis identified two expression patterns (low m6A/high ICP and high m6A/low ICP) with different predicted immune infiltration and responses to ICP inhibitors. A predictive nomogram model to distinguish these 2 clusters was constructed and validated with excellent performance. Conclusion: At the single-cell level, m6A modification facilitates the stemness state in GBM cancer cells and promotes an immunosuppressive microenvironment through ICPs and the GALECTIN signaling pathway network. And we also identified two m6A-ICP expression patterns. These findings could lead to novel treatment strategies for GBM patients.

Are dopamine agonists still the first-choice treatment for prolactinoma in the era of endoscopy? A systematic review and meta-analysis.

BACKGROUND: For prolactinoma patients, dopamine agonists (DAs) are indicated as the first-line treatment and surgery is an adjunctive choice. However, with the development of surgical technique and equipment, the effect of surgery has improved. The aim of this study was to assess the efficacy and safety of surgery versus DAs in patients with different types of prolactinomas. METHODS: A systematic search of literature using Web of Science, PubMed, Cochrane Library, and Clinical Trial databases was conducted until July 12, 2019. Prolactinoma patients treated with DAs (bromocriptine or cabergoline) or surgery (microscopic or endoscopic surgery) were included. Outcomes included the biochemical cure rate, recurrence rate, prolactin level, improvement rates of symptoms, and incidence rates of complications. A random-effects model was used to pool the extracted data. Qualitative comparisons were conducted instead of quantitative comparison. RESULTS: DAs were better than surgery in terms of the biochemical cure rate (0.78 versus 0.66), but surgery had a much lower recurrence rate (0.19 versus 0.57). Full advantages were not demonstrated in improvement rates of symptoms and incidence rates of complications with both treatment options. In microprolactinoma patients, the biochemical cure rate of endoscopic surgery was equal to the average cure rate of DAs (0.86 versus 0.86) and it surpassed the biochemical cure rate of bromocriptine (0.86 versus 0.76). In macroprolactinoma patients, endoscopic surgery was slightly higher than bromocriptine (0.66 versus 0.64) in terms of the biochemical cure rate. CONCLUSION: For patients with clear indications or contraindications for surgery, choosing surgery or DAs accordingly is unequivocal. However, for patients with clinical equipoise, such as surgery, especially endoscopic surgery, in microprolactinoma and macroprolactinoma patients, we suggest that neurosurgeons and endocrinologists conduct high-quality clinical trials to address the clinical equipoise quantitatively.