Volume 38 · Issue 12 · 2022

To investigate the safety and clinical efficacy of extracranial-intracranial (EC-IC) revascularization combined with aneurysm trapping in the treatment of giant intracranial aneurysm (GIAs).

A retrospective study was conducted on 18 cases of GIAs who underwent EC-IC bypass and aneurysm trapping at the Department of Neurosurgery, Nanjing Drum Tower Hospital Affiliated to Nanjing University (6 cases) and the Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University (12 cases) from January 2016 to October 2021. Among them, there were 6 cases of external carotid artery (ECA)-radial artery (RA)-middle cerebral artery (MCA) M2 segment anastomosis, 5 cases of superficial temporal artery (STA)-RA-MCA M2 segment anastomosis, 6 cases of STA-MCA M3/4 segment anastomosis, and 1 case of STA-RA-posterior cerebral artery (PCA) P3 segment anastomosis. The surgical-related complications and efficacy of the patients were retrospectively analyzed.

All patients successfully underwent the operation, and no intracranial aneurysm rupture occurred during the operation. Postoperative imaging examination showed that the intracranial aneurysm disappeared. A total of 5 patients had surgery-related complications within 1 week after the operation, including 4 cases of cerebral infarction, of which 1 case was massive cerebral infarction due to acute bypass graft injury. There was 1 case of oculomotor nerve palsy, while MRI showed no intracranial newly-developed infarction. The median follow-up time after operation was 36 months (3-62 months), and no recurrence of intracranial aneurysm was found in 18 patients. At the latest follow-up, the modified Rankin scale score was 0-1 in 15 cases, 2-3 in 2 cases, and 4-5 in 1 case.

EC-IC bypass combined with aneurysm trapping is an important option to treat GIAs and postoperative brain infraction is the major complication.

To investigate the clinical characteristics and surgical outcomes of intracranial ruptured arteriovenous malformations (AVMs) in children.

From April 2017 to December 2020, the clinical data of 92 children with intracranial ruptured AVMs who underwent microsurgical resection at the Department of Neurosurgery, Children's Hospital of Nanjing Medical University from April 2017 to December 2020 were retrospectively analyzed. According to the urgency of the patient′s conditions, the AVM was resected in 35 patients in acute stage (≤72 h) and in 57 patients (including 12 children with stable condition after emergency treatment) in non-acute phase (≤1 month). Six months after surgery, the modified Rankin Scale (mRS) was used to evaluate the clinical outcomes.

According to the Glasgow Coma Scale (GCS) scores at admission, 10 cases scored 3-5, 16 cases scored 6-8, 17 cases scored 9-12 and 49 cases scored 13-15. 31 cases (33.7%) were complicated with aneurysms and AVM bled again in 4 cases(4.3%) in a short time (≤14 d). According to the Spetzler-Martin grade, 42 cases were grade Ⅰ, 29 cases were grade Ⅱ, 17 cases were grade Ⅲ and 4 cases were grade Ⅳ. The positive rate of AVM in the first angiography was 95.7% (88/92). In 92 cases of AVM resection, 86 cases of AVM were cured by the first resection with the cure rate of 93.5% (86/92). In the acute stage, the cure rate was 94.3% (33/35). There were 2 cases of residual AVM and 3 cases of complications, including hemiplegia, aphasia and epidural hematoma. The cure rate was 93.0% (53/57) in the non-acute stage. There were 4 cases of residual AVM and 4 cases of complications, including 2 cases of aphasia, 1 case of hydrocephalus and 1 case of hemiplegia. All 92 patients were followed up for 6-48 months. At the last follow-up, no recurrence of AVM was found in 92 patients. A total of 89 patients (96.7%) had a favorable outcome(mRS≤2 points) and 3 (3.3%) had a poor outcome(mRS≥3 points).

Children with intracranial ruptured AVMs are in critical condition, a high proportion of whom have combined aneurysms, and they are prone to rebleeding in the short term. Microsurgical resection is an effective treatment method, with a high cure rate and low surgery-related complications.

To investigate the safety and efficacy of real-time fluorescein sodium angiography in surgical clipping of intracranial aneurysm.

The clinical data of 60 patients with intracranial aneurysms who underwent surgical clipping at the Neurosurgery Department of General Hospital of Ningxia Medical University from May 2020 to December 2021 were retrospectively analyzed. There were 63 aneurysms in 60 patients (60 ruptured and 3 with multiple unruptured aneurysms), all of which were anterior circulation aneurysms. The patients underwent routine craniotomy through modified pterional or expanded pterional approach, and fluorescein sodium angiography was used in real-time during aneurysm clipping to evaluate the clipping of aneurysm and the patency of parent artery and perforating artery. Based on the angiography, whether to adjust the aneurysm clip was determined. Postoperatively, cranial CTA was performed to evaluate the clipping of the aneurysm. The patient′s outcome was assessed using the modified Rankin scale (mRS).

All 63 aneurysms were successfully clipped. Intraoperative fluorescein sodium angiography confirmed that 60 (95.2%) aneurysms were clipped completely at one time, the aneurysm sac was not visualized, and the parent artery and perforating artery were well visualized; 1 (1.6%) aneurysm sac was visualized. There was obvious yellow-green fluorescence in the aneurysm, which was considered as incomplete clipping of the aneurysm, and the parent artery was blocked and then re-clipped; 1 (1.6%) aneurysm had residual aneurysm neck, and supplementary clipping was performed; 1 (1.6%) case reported mis-clipping of the branch artery, the aneurysm clip was readjusted, and no ischemic events occurred after the operation. The follow-up time of 60 patients was 5.4±1.1 months (3-24 months), 54 patients (90.0%) had favorable outcomes (mRS: 0-2 points), and 6 patients (10.0%) had poor outcomes (mRS: 3-5 points). From 3 to 24 months after operation, 60 patients underwent re-examination of cranial CTA, and no aneurysm recurrence was found.

Intraoperative real-time fluorescein sodium angiography can evaluate the clipping of aneurysm, which is helpful to adjust the surgical plan in time and ensure the safe and effective completion of intracranial aneurysm clipping.

To investigate the feasibility and safety of Simmons 2 (SIM2) catheter coaxial technology with transradial access (TRA) in the embolization of intracranial unruptured aneurysms.

A retrospective analysis was performed on the clinical data of 32 patients with 37 intracranial unruptured aneurysms treated with endovascular embolization from May to July 2021 at the Department of Neurosurgery, the First Affiliated Hospital with Nanjing Medical University(Jiangsu Province Hospital). All patients underwent the SIM2 (125 cm) catheter coaxial technology to establish surgical channels with TRA. Among them, the target blood vessels included 21 right internal carotid artery, 11 left internal carotid artery, 3 right vertebral artery, and 2 left vertebral artery. There were 10 cases of type Ⅰ aortic arch, 17 cases of type Ⅱ, and 5 cases of type Ⅲ. The success rate of surgical channel establishment, surgery-related complications and aneurysm treatment were summarized and analyzed.

All 32 patients (37 aneurysms) successfully underwent surgical channel establishment and embolization therapy. None of the patients during surgery developed a herniation of the coaxial catheter system into the aortic arch, rupture of the aneurysm, acute thrombosis, or thromboembolic events. Immediately after surgery, there were 17 cases of grade Ⅰ, 14 cases of grade Ⅱ, and 6 cases of grade Ⅲa according to the modified Raymond classification system. On the third postoperative day, one patient showed a right temporal lobe hemorrhage on head CT and was given drug treatment. At the follow-up of 3-6 months after surgery, 32 patients underwent assessment using the modified Rankin scale and there were 29 cases of score 0 and 3 cases of score 1. A total of 25 aneurysms of 23 patients underwent DSA, which demonstrated modified Raymond grade Ⅰ in 21 cases and grade Ⅱ in 4 cases, and no aneurysm recurrence was identified.

The use of SIM2 (125 cm) catheter coaxial technology to establish surgical channel with TRA for the embolization of intracranial unruptured aneurysms has a high success rate and few associated complications, which is suitable for intracranial aneurysm embolization.

To investigate the efficacy and safety of Leo stents in the endovascular treatment (EVT) of intracranial aneurysms.

The clinical data of 152 cases with 174 intracranial aneurysms treated by Leo stents were retrospectively analyzed from August 2019 to August 2021. Among them, 35 patients were treated at the Department of Neurosurgery, Putuo District People′s Hospital, 13 patients at the Department of Neurosurgery, the Third People′s Hospital of Jingdezhen and 104 patients at the Department of Neurosurgery, Huashan Hospital, Fudan University. Clinical and imaging follow-up were performed. The degree of embolization and clinical outcome were assessed by Raymond grade and modified Rankin Scale (mRS) respectively. The mRS score of ≤2 points was defined as good outcome and the mRS score of ≥3 points as poor outcome.

Of 174 aneurysms, 106 (60.9%) were treated by Leo stent-assisted coiling, and the remaining 68 (39.1%) by Leo stents alone. A total of 176 Leo stents were successfully released in 152 patients. Poor opening or anchoring of stents occurred in 9 cases (5.9%) and thrombosis events in 15 cases (9.9%) during procedure. Seven patients (4.6%) developed ischemic symptoms, of which 5 patients (3.3%) had poor outcome during perioperative period. No stent-related bleeding events occurred in 152 cases. Immediate postoperative DSA showed that the rate of excellent embolization(Raymond Ⅰ-Ⅱ)in small and medium aneurysms were 93.8% (60/64) and 90.5% (76/84) respectively, which was significantly higher than that in large or giant aneurysms (42.3%, 11/26) (χ²=41.77, P<0.001). A total of 78 patients(51.3%) with 82 aneurysms had clinical and angiographic follow-up for an average of 11.8±6.5 months (3-23 months) and the rate of excellent embolization remained stable. However, 10 patients(12.8%, 10/78) had an intra-stent stenosis or occlusion of parent artery and 9 of them were asymptomatic. Among the 78 patients, 76(97.4%) had good outcome and 2 (2.6%) had poor outcome.

Leo stent seems safe and effective in the EVT of aneurysms, particularly for small and medium aneurysms. The role of Leo stent still needs to be further studied in other types of aneurysms.

To investigate the efficacy of using flow diverter (FD) alone and that combined with coil embolization in the treatment of medium-sized unruptured intracranial aneurysms.

A retrospective analysis was conducted on the clinical data of 137 patients with a total of 155 medium-sized (5-15 mm) unruptured intracranial aneurysms who were treated with FD alone or that combined with coil embolization at the Department of Neurosurgery of Henan Provincial People′s Hospital from March 2015 to September 2020. According to the treatment methods, all patients were divided into FD group (96 cases) and FD+ coil group (41 cases). The modified Rankin scale (mRS) was used to evaluate the outcome at the 6-month postoperative follow-up (≤2 was considered as favorable outcome). The digital subtraction angiography (DSA) was re-examined 6 months after the operation, and O′Kelly-Marotta (OKM) grading scale was used to evaluate the outcome of aneurysm occlusion (class C and D as satisfactory occlusion). The baseline data, postoperative complications, mRS at discharge and aneurysm occlusion during follow-up were analyzed and compared between the two groups.

There were no significant differences in baseline data such as gender, age, and aneurysm characteristics between the two groups (all P>0.05). A total of 161 FDs were implanted in 155 aneurysms in 137 patients. In the FD+ coil group, the coil packing density [M (Q₁, Q₃)] was 11.5% (10.2%, 15.5%). Compared with the FD+ coil group, the proportion of patients with the mRS of 0-2 points at discharge [99.0% (95/96) vs. 97.6% (40/41)] and the incidence of postoperative complications [4.2% (4/96) vs. 7.3% (3/41)] in the FD group were not statistically significant (both P>0.05). At 6 months post operation, 127 patients were followed up, and there was no significant difference in the proportion of patients with favorable outcomes between the two groups [98.9% (88/89) vs 100% (38/38), P=0.999]. A total of 109 aneurysms of 98 patients were followed up by imaging, and the median follow-up time was 6 months. Compared with the FD group, the satisfactory occlusion rate of the FD+ coil group was higher, and the difference was statistically significant [94.1% (32/34) vs. 74.7% (56/75), χ²=5.69, P=0.017].

Treatment using FD combined with coils for medium-sized unruptured intracranial aneurysms is associated with a higher rate of complete occlusion of aneurysms compared with that using FD alone, and it does not increase the risk of complications.

To compare the effects of balloon guide catheter (BGC) and conventional guide catheter (CGC) on treatment outcomes in patients with anterior circulation acute ischemic stroke treated with intracranial support catheter combined with stent thrombectomy (SWIM) technique.

The clinical data of 198 patients with anterior circulation acute ischemic stroke admitted to the Interventional Radiology Department of the First Affiliated Hospital of Soochow University from January 2017 to June 2021 were retrospectively analyzed. All patients were treated with SWIM technology. The patients were divided into BGC group and CGC group according to the type of guiding catheter used. After obtaining well balanced samples by the 1 ∶1 propensity matching method, the differences in first complete recanalization, final recanalization, the procedure time, embolus escape, hemorrhagic transformation, 90-day clinical favorable outcome, 90-day all-cause mortality and complications were analyzed between the two groups were compared.

Among 198 patients, BGC group had 46 patients, CGC group had 152 patients and 86 matched pairs could be identified. No statistical difference was found in first complete recanalization [32.6% (14/43) vs. 32.6% (14/43), matched RR=1.00, 95%CI: 0.64-1.57], final recanalization [90.7% (39/43) vs. 90.7% (39/43), matched RR=1.00, 95%CI: 0.48-2.07], the procedure time (100.3±3.4 min vs. 100.5±6.9 min, P=0.984), embolus escape rate [9.3% (4/43) vs. 7.0% (3/43), matched RR=1.18, 95%CI: 0.49-2.86], hemorrhagic transformation rate [18.6% (8/43) vs. 16.3% (7/43), matched RR=1.09, 95%CI: 0.60-1.96], 90-day favorable outcome rate [55.8% (24/43) vs. 41.9%(18/43), matched RR=1.48, 95%CI: 0.93-2.34], 90-day all-cause mortality rate [20.9% (9/43) vs. 9.3%(4/43), matched RR=1.74, 95%CI: 0.75-4.03], complications rate [7.0% (3/43) vs. 4.7% (2/43), matched RR=1.27, 95%CI: 0.42-3.78] between two groups(all P>0.05).

For patients with anterior circulation acute ischemic stroke, when the technique of SWIM is used as the first-line treatment, there seems no significant difference in the therapeutic effect between BGC and CGC.

To preliminary investigate the clinical efficacy of non-acute endovascular recanalization therapy for symptomatic atherosclerotic vertebrobasilar artery occlusion (VBO).

A retrospective analysis was conducted on the clinical data of 58 patients with non-acute symptomatic atherosclerotic VBO who underwent endovascular surgery at the Department of Cerebrovascular Diseases, People′s Hospital of Zhengzhou University from January 2019 to December 2020. Preoperative assessment using the modified Rankin scale (mRS) showed 0-2 in 50 cases and 3-4 in 8 cases. Vascular recanalization, perioperative complications, and postoperative follow-up results were documented.

Among the 58 patients, 48 (82.8%) had successful vascular recanalization, and immediate postoperative angiography showed that 26 (54.2%) were grade 3 and 22 (45.8%) were grade 2b based on the modified thrombolysis in cerebral infarction (mTICI) scale. Ten patients (17.2%) failed to finish the treatment because the microguide wire could not pass through the occluded segment. Among the 48 patients who successfully underwent recanalization, 2 (4.2%) had ischemic stroke perioperatively, and 1 of them showed a new infarct on MRI; 1 case (2.1%) developed cerebral hemorrhage. None of the 10 patients who had unsuccessful recanalization developed surgery-related complications. At 3-6 months post surgery and among 48 patients with successful recanalization, DSA showed that 2 cases (4.2%) developed stent occlusion (both reported perioperative ischemic stroke); 6 cases (12.5%) had restenosis in the stent, but none were clinically symptomatic. The mRS score was 0-2 in 47 patients (97.9%) and and 4 in 1 patient who developed recurrent cerebral infarction due to stent occlusion. All 10 patients who failed to undergo recanalization were treated with medication, all had symptoms of ischemic stroke, and 2 cases had worsening symptoms.

Patients with non-acute atherosclerotic VBO have a higher success rate of vascular recanalization, a lower incidence of surgery-related complications, and a relatively good short-term clinical outcome.

To explore the relationship between the expression of annexin A2 (ANXA2) and peritumoral brain edema (PTBE) in adult-type diffuse cerebral gliomas.

The clinical data of 42 patients with adult-type diffuse gliomas who underwent tumor resection at the Department of Neurosurgery, Peking University Third Hospital from June 2020 to August 2021 were retrospectively analyzed. All patients were classified into mild, moderate and severe PTBE types according to edema index (EI) measured by preoperative head MRI. The expression of ANXA2 in PTBE region was detected by immunohistochemical staining (IHC), and the IHC score was calculated. Patients were divided into high expression group (IHC score ≥ 6) and low expression group (IHC score < 6) to compare the degree of PTBE between the two groups. Univariate and multivariate logistic regression analysis and Spearman correlation analysis were used to evaluate the relationship between ANXA2 and PTBE degree.

The degree of PTBE was significantly different between ANXA2 high expression group (n=26) and ANXA2 low expression group (n=16)(P=0.001), and the proportion of severe edema was higher in ANXA2 high expression group. The univariate logistic regression analysis showed that highly-expressed ANXA2 (OR=14.44, 95%CI: 3.40-80.82, P=0.001) and high grade of World Health Organization (WHO) glioma grade (OR=14.45, 95%CI: 3.41-80.82, P=0.001) were the influencing factors of severe PTBE. Multivariate logistic regression analysis confirmed that highly-expressed ANXA2 (OR=19.48, 95%CI: 2.88-253.96, P=0.007) and high grade of WHO glioma classification (OR=19.15, 95%CI: 2.91~233.86, P=0.006) were independent risk factors for severe PTBE, while male, age at diagnosis ≥ 45 years old, maximum diameter of tumor >5 cm , IDH mutation status or others were not influencing factors (P>0.05). EI was correlated with the IHC score of ANXA2 in a positive linear correlation (r=0.72, P<0.05).

Adult-type diffuse glioma patients with high expression of ANXA2 in the PTBE region have a high risk of severe PTBE, and the degree of PTBE increases with the enhancement of ANXA2 expression level.

To investigate the clinical characteristics, treatment and prognostic factors of primary spinal cord glioblastomas (GBMs).

The clinical data of patients with primary spinal cord GBMs admitted to the Department of Neurosurgery, Beijing Tsinghua Chang Gung Hospital from May 2015 to July 2019 were analyzed retrospectively, which accounted for 3.6% (11/308) of spinal cord tumors during the same period at our hospital. All patients received surgery, 2 patients received postoperative radiotherapy and chemotherapy, 3 patients received chemotherapy only, 6 patients did not receive adjuvant therapy, and 2 patients received bevacizumab salvage therapy after tumor recurrence. Clinical follow-up was performed after surgery. Kaplan-Meier analysis was used to evaluate the survival of patients, and the log-rank test was used to compare the groups to explore the influencing factors of the survival of patients with primary spinal cord GBMs.

Among the 11 patients, subtotal resection was achieved in 8 patients and partial resection in 3 patients. After a median follow-up of 13.2 months (range: 1-33 months), 10 patients died and 1 patient survived. The median progression-free survival (PFS) and overall survival (OS) were 6.0 months and 12.0 months, respectively. Log-rank univariate analysis showed that duration of the preoperative symptoms and the number of spinal segments involved by tumor were both confirmed as factors that may influence PFS and OS (all P<0.05). Moreover, the age at diagnosis may affect PFS (P=0.049) and Ki-67 index may affect OS (P=0.043).

Primary spinal cord GBMs are extremely rare with malignant features and dismal prognosis. Early surgical decompression combined with adjuvant therapy such as radiotherapy and chemotherapy and bevacizumab is the treatment strategy. The survival time of primary spinal cord GBM patients is short. Short disease duration, high number of tumor segments, high Ki-67 proliferation index, and young age suggest a poor prognosis for patients.

To investigate the surgical effect of hypoglossal-facial nerve side-to-end neurorrhaphy in the treatment of severe peripheral facial paralysis after acoustic neuroma and the changes of related electrophysiological indicators.

The clinical data of 35 patients with severe peripheral facial paralysis after acoustic neuroma surgery who were admitted to the Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from February 2018 to December 2020 were retrospectively analyzed. A total of 24 cases of facial nerve electrophysiological examination were performed before operation. Hypoglossal nerve-facial nerve side-to-end neurorrhaphy was performed in all patients. House-Brackmann (H-B) facial nerve function grading, Sunnybrook facial nerve rating scale (Sunnybrook score), facial nerve electrophysiological exams (including blink reflex, facial nerve electrogram, fibrillation potential, positive sharp wave, motor unit potential) were used before surgery, 6 months and 12 months after surgery to comprehensively evaluate the facial nerve function of patients.

After 6 months of follow-up, 29 (82.9%) patients′ static face and expression were significantly recovered. H-B grade and Sunnybrook score were significantly improved compared with those prior to operation (both P<0.001). At 12 months after operation, H-B grade and Sunnybrook score were significantly improved compared with those at 6 months after operation (both P<0.001) A total of 23 patients underwent electrophysiological follow-up (1 case was lost to follow-up). No ipsilateral R1 or R2 wave was detected before operation and 6 months after operation, and the proportion of blink reflex elicited at 12 months after operation was significantly increased compared with that before operation (P<0.001). The amplitude of facial electrogram at 6 months and 12 months post operation was significantly increased, and the fibrillation potential and positive sharp wave grade were significantly decreased (all P<0.05). At 12 months post operation, the motor unit potential amplitude of orbicularis oris muscle and orbicularis oculi muscle were significantly higher than those before operation (both P<0.05).

The hypoglossal-facial nerve side-to-end neurorrhaphy can effectively promote the recovery of severe peripheral facial paralysis after acoustic neuroma surgery, among which the orbicularis oris and orbicularis oculi muscles have the most significant improvement.

To investigate the effect of human acellular allogeneic dermal matrix in the repair of dural defects.

A randomized parallel controlled clinical study was conducted. From May 2015 to September 2018, 53 patients in Department of Neurosurgery, Huashan Hospital of Fudan University and 35 patients in Department of Neurosurgery, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine were enrolled into this study. All 88 patients were randomly assigned to the experimental group (n=45) and the control group (n=43). The dural defect was repaired with human acellular allogeneic dermal matrix in the experimental group and with porcine biotype dural mesh in the control group. The surgeon evaluated the toughness, ductility, and suturing ability of the material. The negative pressure ball drainage volume and the occurrence of adverse events was followed up regularly in hospital or outpatient department after operation. CT or MRI was performed 10 days, 3 months and 6 months after operation to observe the epidural effusion and subcutaneous effusion in the operation area to determine whether there was cerebrospinal fluid leakage. The baseline data, intraoperative material evaluation results and postoperative adverse events were compared between the two groups.

There was no significant difference in the age, gender or other baseline data between the two groups (P>0.05) which were comparable. There was no significant difference in the volume of negative pressure ball drainage at 24 h after operation between the two groups (P=0.977). Postoperative wound healing was grade Ⅰ in both groups, and there was no subcutaneous effusion or cerebrospinal fluid leakage. At the end of 6 months after operation, the latest imaging examination of the two groups of patients showed that there was no abnormal signal in the area of dural repair. There were no significant differences in the incidences of general adverse events [62.2% (28/45) vs 48.8% (21/43)] and serious adverse events [6.7% (3/45) vs 4.6% (2/43)] between the experimental group and control group (both P>0.05). There were no adverse events related to artificial repair materials in either group. The surgeons were more satisfied with the toughness, ductility and suturing of the artificial repair material in the experimental group than those in the control group (all P<0.05).

Human acellular allogeneic dermal matrix material has good toughness, extensibility and suturing ability in the repair of dural defect. Its repair effect is similar to that of conventional dural mesh, and does not increase the incidence of postoperative adverse events.

To investigate the expression of TrxR1 gene in glioma tissue and its effect on biological characteristics of glioma cell line U87.

Transcriptome and clinical data of glioma samples from 325 glioma patients in the Chinese Glioma Genome Atlas Project (CGGA) database were retrospectively analyzed, and the expression of TrxR1 in normal brain tissue and glioma tissue was further detected by western blot, RT-PCR and immunohistochemical techniques. A total of 12 cases of glioma and 12 cases of normal brain tissues were collected from patients with glioma and spontaneous intracerebral hemorrhage who underwent surgical treatment at the Neurosurgery Department of Tianjin Medical University General Hospital from September 2010 to November 2018. Glioma cell line U87 was cultured and divided into control, nonsense sequence and siRNA TrxR1 groups. The expression of TrxR1 gene was detected by RT-PCR, Western blot and immunohistochemistry. MTT and Transwell assays were used to detect the proliferation and invasion of glioma cell line U87. The spheroidization assay was used to detect the tumorigenicity of U87 cell line. Western blot was used to detect the effect of TrxR1 knockdown on STAT3 expression and the STAT3 signaling pathway related genes.

Analysis of the CGGA database showed that the expression of TrxR1 mRNA increased with the increase of the pathological grade (WHO grade) of glioma(P<0.01), and the overall survival of patients in the high expression group was lower than that in the low expression group (P=0.019). Western blot, RT-PCR and immunohistochemical experiments showed that compared with normal brain tissue, the expression of TrxR1 in glioma tissue was significantly increased (all P<0.01). The siRNA TrxR1 could effectively downregulate TrxR1 gene expression. Compared with the control and nonsense sequence groups, siRNA TrxR1 group significantly reduced TrxR1 expression at both protein and mRNA levels (P<0.05). The results of MTT showed that the growth of glioma cells was significantly inhibited by knockdown of TrxR1 expression, and the cell proliferation rate was only 39.3% on the fourth day. The results of Transwell experiment showed that the number of cells passing through the chamber membrane in the siRNA TrxR1 transfection group was lower than that in the control group and the nonsense sequence group (both P<0.01), which was only 47.0% of the control group. The results of spheroidization assay showed that the spheroidization efficiency of glioma stem cell was significantly decreased after TrxR1 knockdown (P<0.01). WB detection results showed that the expression levels of p-STAT3 (Tyr705), Bcl-xl and Cyclin D1 in siRNA TrxR1 group were significantly lower than those in control group and nonsense sequence group (all P<0.01). However, the expression level of STAT3 did not change significantly (P>0.05).

The expression of TrxR1 gene is up-regulated in glioma tissues, and TrxR1 plays a role of oncogene. The mechanism may be related to the activation of STAT3 signaling pathway by regulating the phosphorylation of STAT3. Therefore, TrxR1 may become a new therapeutic target for gliomas.

To screen 1p/19q co-deletion feature gene in gliomas based on machine learning and to explore its role in predicting 1p/19q co-deletion.

Retrospective analyses of glioma tissues transcriptome sequencing data and corresponding clinical information of glioma patients in Chinese Glioma Genome Atlas Project (CGGA) and The Cancer Genome Atlas (TCGA) databases were performed. The CGGA_693 (508 cases) was used as training cohort, while CGGA_325 (298 cases) and TCGA (545 cases) were used as testing groups. Univariate Cox regression and machine learning methods (Lasso regression and support vector machine recursive feature elimination, SVM-RFE) were used to screen immune-related and differentially expressed prognostic genes between 1p/19q co-deletion and 1p/19q non-co-deletion groups in the test cohort. The intersected genes from the above two methods were identified as candidate 1p/19q co-deletion feature genes (" feature genes" ). Receiver operator characteristic (ROC) curves and the area under the curves (AUCs) of the 1p/19q co-deletion feature genes were analyzed in the training and testing cohorts. The Kaplan-Meier survival curves were used for analyzing the relationship between prognosis and feature genes with higher AUC value. Logistic regression was used to establish models for predicting 1p/19q co-deletion based on feature genes and corresponding clinical features in the training cohort. AUC, Akaike′s Information Criterion (AIC), Net reclassification index (NRI), integrated discrimination improvement (IDI), decision curve analysis (DCA) and other indicators were used to evaluate the prediction efficiency of the models. In addition, 22 glioma samples extracted from the surgery at the Department of Neurosurgery, the Affiliated Changzhou Second People′s Hospital of Nanjing Medical University, were used for testing the expression of mRNA of feature gene.

A total of 6 feature genes, including angiopoietin like 2 (ANGPTL2), bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 8b (BMP8b), fibroblast growth factor 11 (FGF11), histone deacetylase 1 (HDAC1) and α-taxilin (TXLNA) were screened in the testing cohort. The differential expression of 6 feature genes between 1p/19q co-deletion and non-co-deletion groups was statistically significant in the testing cohorts. The ROC of three groups indicated that the AUC values of predicting 1p/19q co-deletion by HDAC1, or TXLNA were larger than 0.9. Survival analyses showed that the overall survival (OS) of patients with lower expression of HDAC1 or TXLNA was better than that of higher expression, and the difference was statistically significant (both P<0.001). Three models for predicting 1p/19q co-deletion were established. They were model A (variable: TXLNA), model B (variable: TXLNA, HDAC1) and model C (variable: TXLNA, HDAC1, age, WHO grade and IDH mutation status). Several effective prediction indicators showed that the ability of prediction for 1p/19q co-deletion of model A was poor than that of model B and model C, but the difference was slight. The expression of mRNA of TXLNA was lower in the 1p/19q co-deletion group.

TXLNA is a feature gene of 1p/19q co-deletion in gliomas and it has a high efficiency in predicting 1p/19q co-deletion.