Volume 36 · Issue 08 · 2020

hypertensive intracerebral hemorrhage (HICH) refers to the sudden occurrence of cerebral parenchymal hemorrhage in the basal ganglia, thalamus, ventricles, cerebellum and brainstem in patients with a clear history of hypertension, and secondary cerebral hemorrhage caused by trauma, vascular structural abnormalities, coagulation dysfunction, hematological diseases, systemic diseases and neoplastic diseases is excluded. HICH has the characteristics of high morbidity, mortality, disability and recurrence. The prevention and treatment of HICH requires the cooperation of emergency department, imaging department, neurology department, neurosurgery department, critical care department and rehabilitation department. In 2015, the Neurosurgery Branch of the Chinese Medical Association, the Emergency Physician Branch of the Chinese Medical Association, and the Stroke Screening and Prevention Engineering Committee of the National Health and Family Planning Commission organized domestic multidisciplinary experts to jointly formulate the "Chinese Multidisciplinary Expert Consensus on the Diagnosis and Treatment of Spontaneous Cerebral Hemorrhage"^[1]It has played an important role in guiding and standardizing the diagnosis and treatment of spontaneous intracerebral hemorrhage (SICH) in China. In the past five years, with a large number of multidisciplinary research progress and the publication of new evidence-based medical evidence, according to China's basic national conditions, upgrading the consensus to guidelines will help domestic medical units at all levels to make better decisions in the process of clinical practice. This guide mainly introduces HICH, which is the most common and controversial in diagnosis and treatment of SICH in China^[2,3]and recommended with reference to the level of evidence of the 2015 American Heart Association/American Stroke Association (AHA/ASA) SICH guidelines. Recommended levels: Grade I should be implemented, Grade IIA is appropriate for implementation, Grade IIB is considerable, and Grade III is unhelpful or harmful; Level of evidence: Grade A is multicenter or multiple randomized controlled trials, Grade B is single-center single-item randomized controlled trials or multiple non-randomized controlled trials, Grade C is expert opinion, case study.

To investigate the evolution of postoperative hypernatremia for sellar tumor patients and risk factors for the severity of hypernatremia.

From January 2016 to December 2018, a total of 2 494 patients with sellar tumors underwent surgery at Department of Neurosurgery, Peking Union Medical College Hospital. Among them, 578(23.2%) patients developed postoperative hyperna-tremia. The patients were divided into mild (533 cases), moderate (30 cases), and severe (15 cases) groups according to the severity of hypernatremia. We retrospectively analyzed the patient’s outcome and risk factors for the severity of hypernatremia.

Of 578 patients, the median time for first development of postoperative hypernatremia was 2 days post operation. A total of 541 cases (93.6%) had hypernatremia within 3 days after surgery and included 74 (12.8%) with hyponatremia for a certain period. Before discharge, 295 (51.0%) patients returned to the normal sodium level, 267 (46.2%) were diagnosed as hypernatremia and 16 (2.8%) were diagnosed as hyponatremia. A total of 441 (76.3%) patients developed diabetes insipidus (DI). Among the 192 DI patients whose DI was resolved, 98 (51.0%) patients returned to the normal sodium level. Among the remaining 249 patients whose DI was unresolved, 128 (51.4%) patients returned to the normal sodium levels. There was no significant difference in the outcome of hypernatremia between the DI-resolved group and DI-unresolved group (P=0.801). Univariate analysis revealed a significant difference between various severity groups of hypernatremia in sex ratio, disease type distribution, operation type distribution, incidences of DI and intracranial infection, urine volume, operation time, intraoperative blood loss, and tumor volume (all P<0.05). Multivariate analysis results indicated that large tumor (OR=1.697, 95% CI: 1.241-2.318, P=0.001), postoperative intracranial infection (OR=3.661, 95% CI: 1.320-10.155, P=0.013) and Cushing′s disease (OR=3.366, 95% CI: 1.051-10.794, P=0.041) were independent influencing factors for the severity of hypernatremia.

Postoperative patients with sellar tumors seem to show a high incidence of hypernatremia and have a high proportion of cases developing DI. However, the recovery of DI has little effect on the outcome of hypernatremia and is not the independent influencing factor for the severity of hypernatremia. Large tumor, Cushing′s disease and postoperative intracranial infection are the independent risk factors for the severity of hypernatremia.

To investigate the incidence and related factors of venous thromboembolism (VTE) developed during treatment of traumatic intracranial hemorrhage.

The clinical data of 362 patients with isolated traumatic intracranial hemorrhage (multiple injuries excluded) treated at Department of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University from May 2017 to October 2019 were analyzed retrospectively. During hospitalization, patients with clinical high-risk for VTE or those of highly suspected VTE were evaluated by color Doppler ultrasound or chest spiral CT scan, and were divided into no-VTE group and VTE group. The incidence of VTE and related risk and protective factors were investigated by univariate and multivariate logistic regression analysis.

Among 362 patients with merely traumatic intracranial hemorrhage, a total of 160 patients developed VTE, with an overall incidence of 44.2%. The result of logistic regression analysis showed that older age (40-59 years, OR=5.316, 95% CI: 2.322-11.173, ≥60 years, OR value=11.221, 95% CI: 4.935-25.518) and blood transfusion treatment after admission (OR=2.396, 95% CI: 1.413-4.063) were risk factors for VTE (all P<0.05). Inpatients were treated with different measures to prevent possible VTE, which included active/passive activities in 158 cases (43.7%), using lower limb elastic socks in 104 cases (28.7%), and using mechanical intermittent air pump for lower extremities in 100 cases (27.6%). The result of logistic regression analysis showed that using mechanical intermittent air pump for lower extremities (OR=0.245, 95% CI: 0.132-0.452) was a protective factor for VTE (P<0.05).

Patients with traumatic intracranial hemorrhage have a high incidence of VTE, which is one of the most important complications. Older patients (over 40 years of age) admitted to hospital and those receiving blood transfusions are more likely to develop VTE. Early use of lower limb mechanical air pumps can significantly reduce the incidence of VTE.

To investigate the role of arterial lactic acid level in patients with aneurysmal subarachnoid hemorrhage (aSAH).

A retrospective study was conducted on the clinical data of 166 patients with aSAH admitted to Neurosurgery Department of Xuanwu Hospital, Capital Medical University from January 2018 to October 2018. Among them, the aneurysm responsible for aSAH were located in the anterior circulation in 136 cases, and in the posterior circulation in 30 cases. Craniotomy and surgical clipping were performed in 57 cases, intravascular intervention treatment in 99 cases, intravascular intervention therapy plus surgical clipping in 2 cases, and conservative treatment of medication in only 8 cases. According to the highest blood lactic acid level within 72 h post admission to intensive care unit, the normal lactic acid group (blood lactic acid ≤ 2.2 mmol/L) and elevated lactic acid group (blood lactic acid > 2.2 mmol/L) were divided. The Glasgow Outcome Scale (GOS) was used to assess the patient′s outcome: 1-3 as poor and 4-5 as good. Between the 2 groups, the differences in the Hunt-Hess grade at admission, location of aneurysm responsible for aSAH, occurrence of complications and outcome were compared. The risk factors affecting the prognosis of aSAH patients were evaluated by using univariate and multivariate logistic regression analysis.

Of the 166 patients, 54 (32.5%) showed elevated level of lactic acid, and the differences in underlying diseases, location of aneurysm responsible for aSAH and treatment methods were not statistically significant (all P>0.05). The difference between elevated lactic acid group and normal lactic acid group in the Hunt-Hess grade at admission was significant (P<0.001). The incidences of cerebrovascular spasms, delayed cerebral ischemia (DCI), hypoalbuminemia and anemia in the elevated lactic acid group were higher than those in the normal lactic acid group, and the differences were statistically significant (allP<0.05). The results of univariate analysis showed that the Hunt-Hess grade at admission, cerebrovascular spasms, DCI, hypoalbuminemia, anemia, the level of arterial blood lactic acid were the clinical factors that affected the prognosis of aSAH patients (allP<0.05). Multivariate logistic regression analysis results showed that the Hunt-Hess grade at admission (OR=4.424, 95% CI: 1.029-19.025, P=0.046), cerebrovascular spasms (OR=4.140, 95% CI: 1.197-14.326, P=0.025), hypoalbuminemia (OR=5.385, 95% CI: 1.142-25.396, P=0.033), anemia (OR=8.341, 95% CI: 1.579-44.051, P=0.012) and arterial blood lactic acid level (OR=7.997, 95% CI: 2.313-27.651, P=0.001) were the independent influencing factors for the prognosis of aSAH patients.

The arterial lactic acid level post aSAH may be related to the Hunt-Hess grade at admission, complications such as cerebral vasospasm and DCI, and might be a risk factor that affects the prognosis of patients with aSAH, might be able to serve as a biomarker of aSAH severity and prognosis.

To elucidate the clinical and radiologic features and treatment of patients with bilateral chronic subdural hematomas (CSDH) complicated by spontaneous intracranial hypotension (SIH).

A retrospective study was conducted on the data of 14 patients with bilateral CSDH combined with SIH who were admitted to Neurosurgery Department, Shanghai Tenth Hospital, Tongji University from January 2016 to January 2020. All the patients had an initial Glasgow Coma Score (GCS) greater than or equal to 13. All patients underwent CT and MRI examination of the skull before operation, and 5 patients underwent cerebrospinal fluid (CSF) pressure measurement through lumbar puncture. Treatment methods included conservative treatment (6 cases) and surgical operation (8 cases). For surgical operation, burr hole drainage was performed. Glasgow Outcome Scale (GOS) was used for the outcome assessment.

Among the 14 patients, orthostatic headache was the most common characteristic symptom of SIH(10 cases). Diffuse dura enhancement on contrast-enhanced MRI was the most typical imaging feature(12 cases). The symptoms of all 6 patients undergoing conservative treatment were signiciantly improved post medication. Re-examination of CT or MRI showed that the hematoma disappeared or shrank significantly. Of the 8 patients undergoing burr-hole drainage, 3 experienced a rapid postoperative deterioration of neurological functions, and 1 died post operation. At the time of discharge, the conditions of 13 patients were all significantly improved after treatment according to the diagnosis of SIH, and the GOS ratings were all grade Ⅴ. The follow-up time of 13 patients was 24.6±14.9 months (4-52 months). No recurrence of hematoma or related symptoms was reported.

The major clinical and imaging features of bilateral CSDH complicated by SIH are orthostatic headache and diffuse enhancement of the dura mater respectively. Clinically, conservative treatment or drilling and drainage should be selected according to the individual situation of the patient.

To explore the effect of nasogastric tube decompression combined with nasointestinal tube nutrition support in enhanced postoperative recovery in critically ill patients with neurosurgical diseases.

We retrospectively analyzed the clinical data of a total of 218 critically ill neurosurgical patients admitted to Department of Neurosurgery, Tangdu Hospital, Air Force Medical University. Among those, 105 patients received nasogastric tube decompression and nutritional support from January 2017 to May 2018 (group A), and 113 received nasogastric tube decompression combined with nasointestinal nutrition support from June 2018 to October 2019 (group B). The nutritional risk assessment was performed, and the parameters were compared between the 2 groups including the serum albumin, total protein and hemoglobin. The rate of postoperative complications, average length of stay, stay at neurosurgical intensive care unit (NICU), and treatment costs were analyzed.

There was no significant difference in age, gender, preoperative diagnosis, surgical methods, preoperative Glasgow coma score, acute physiology and chronic health evaluation scoring system Ⅱ score, nutrition risk screening score summary table (2002) score, or body mass index between group A and B (all P>0.05). There were no statistically significant differences between the 2 groups in laboratory indicators on the day of tube placement (allP>0.05). Compared with those in group A, the serum albumin (30.3±4.5 g/Lvs. 28.4±3.3 g/L, P=0.001), total protein (64.7±5.0 g/L vs. 63.0±4.2 g/L, P=0.010) and the intake of nutrient solution in group B were higher (P<0.001), and the amount of infusion in group B was lower 7 days after tube placement (P<0.001). At 14 days after tube placement, the serum albumin level in group B (33.2±3.7 g/Lvs. 31.1±4.2 g/L, P=0.009) was higher than that in group A, and the infusion volume was lower(P=0.001). Postoperatively, in group B, the incidences of vomiting [22.1% (25/113) vs. 37.1% (39/105), P=0.015] and aspiration [9.7% (11/113) vs. 21.9% (23/105), P=0.013] were decreased compared with those in group A. The NICU stay in group B (7.6±4.2 d vs. 9.1±5.1 d, P=0.019) and the cost of non-surgical treatment (7.12±3.58 ten thousand yuans vs. 9.72±5.37 ten thousand yuans, P<0.001) were less than those in group A.

With the protocol of enhanced postoperative recovery, the application of nasogastric tube decompression combined with nasointestinal tube nutrition support could significantly improve the nutritional status, reduce related complications, and promote enhanced recovery in critically ill neurosurgical patients. In addition, the NICU stay and non-surgical treatment costs are also effectively reduced.

To evaluate the clinical value of transcranial doppler ultrasound (TCD) in evaluation of neurofunctional deterioration (ND) in patients with moderate traumatic brain injury (mTBI).

A retrospective study was performed on 88 patients with mTBI admitted to Department of Neurosurgery, the Second Affiliated Hospital, Airforce Military Medical University from October 2012 to June 2017. The 88 patients had a Glasgow coma score (GCS) of 10.3±1.1 points (9-12 points) at admission. They were reassessed every 8 hours. ND was defined as a decrease in GCS of more than 2 points or rapid development requiring immediate surgical treatment. After admission, all patients were monitored by TCD for cerebral hemodynamic parameters of bilateral middle cerebral arteries. Univariate and multivariate logistic regression analyses were conducted to determine the clinical factors that affected ND. Furthermore, the receiver operating characteristic curve (ROC) was drawn and the area under the curve (AUC) was calculated for evaluation of the diagnostic efficacy of independent risk factors that affected the patients′ ND.

Of the 88 patients, 40 developed ND, while the other 48 did not. Univariate analysis showed that age, GCS score at admission, CT grade and cerebral hemodynamic parameters (PI, FVd, FVs, FVm) may be influencing factors for ND in patients with mTBI (all P<0.05). Furthermore, multivariate logistic regression analysis showed that FVd (OR=0.873, 95% CI: 0.816-0.921, P<0.001), FVs (OR=1.061, 95% CI: 1.026-1.104, P=0.001) and PI (OR=80.700, 95% CI: 1.600-716.200, P<0.001) were independent risk factors that affected ND in patients with mTBI. By plotting ROC, we found that the highest diagnostic efficiency was PI (AUC=0.869), followed by FVd (AUC=0.827); the optimal cut-off values were PI>1.22 and FVd<35 cm/s.

As a noninvasive, repeated, bedside assessment tool, cerebral hemodynamic parameters of TCD can be effective predictive factors of ND in patients with mTBI.

To explore the value of hybrid intraoperative evaluation technique in treatment of complex intracranial aneurysms.

A retrospective analysis was conducted on the clinical data of 20 patients with 20 complex intracranial aneurysms who underwent adjustment of treatment strategy based on intraoperative evaluation during hybrid operation at Department of Neurosurgery, Huashan Hospital, Fudan University between November 2016 and December 2018. For the 20 patients, the original surgical plan included craniotomy plus aneurysm clipping (8 cases), extracranial-intracranial bypass plus aneurysm trapping or proximal occlusion of parent artery (9 cases) and balloon-assisted clipping (3 cases). Those plans were adjusted according to the results of intraoperative evaluation such as morphological observation, blood flow analysis by DSA and neurophysiological monitoring. The cause of adjustment, corresponding strategies, surgical results and outcome were analyzed according to the characteristics of aneurysms. The outcome was evaluated based on the modified Rankin scale (mRS).

Among the 20 cases, the causes of adjustment included calcification in the aneurysm neck resulting in clipping failure (2 cases), difficulty in proximal occlusion of blood flow (2 cases), aneurysm residue (6 cases), parent artery stenosis (2 cases) and blood flow evaluation after proximal occlusion or trapping (8 cases). The surgical strategy was changed to endovascular embolization in 4 cases, the site of aneurysm clipping was adjusted in 5, the pattern of blood flow reconstruction was changed in 7, the choice of proximal occlusion or distal occlusion was made based on intraoperative blood flow occlusion test in 3, and additional aneurysm wrapping was applied in 1. There were 17 aneurysms completely occluded and 3 aneurysms which had partial residue. One patient with ruptured aneurysm died at 5 days post operation due to severe cerebral vasospasm. Five patients developed dysfunctions in the contralateral limbs post operation. No newly-developed neurologic dysfunction was reported in 19 patients at 6 months after operation. Aneurysm recurrence was indicated in 1 patient with giant cavernous sinus aneurysm who had residue post operation. The mRS score was 0 in 14 patients, 3 in 1, 4 in 3 and 5 in 1.

Under a hybrid operation mode, intraoperative evaluation could timely reveal intraoperative abnormalities, provide accurate blood flow assessment, help optimize the surgical strategy and thus improve the patient′s outcome.

To explore the characteristics of water and sodium imbalance in children with craniopharyngiomas and its relationship with the dysfunction of hypothalamus and hypophysis.

From January 2015 to January 2019, the clinical data of 102 children with craniopharyngioma admitted to Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University were retrospectively analyzed. All the children underwent surgery prior to their admission. The conditions of pituitary target gland axis function and water and sodium abnormalities were evaluated before and after surgery, and the relationship between the imbalance of sodium and water and the abnormal function of hypothalamus and pituitary was analyzed.

Among 102 children, 38 (37.3%) cases had central diabetes insipidus (CDI), 41(40.2%) cases had impaired pituitary-thyroid axis (IPTA), 35 (34.3%) cases had impaired pituitary-adrenal axis (IPAA), 35 (34.3%) cases had hypernatremia, and 6 (5.9%) cases had hyponatremia before operation. There were 76 (74.5%) cases of CDI, 88 (86.3%) cases of IPTA , 82 (80.4%) cases of IPAA, 60 (58.8%) cases of hypernatremia, and 16 (15.7%) cases of hyponatremia post operation. The differences between the ratios before and after operation were statistically significant (all P<0.05). The levels of serum cortisol, free triiodothyronine, free thyroxine and thyroid stimulating hormone decreased after operation compared to those before operation (allP≤0.01). The ratios of hypernatremia, hyponatremia and normal blood sodium in patients with CDI, IPTA and IPAA were different either prior to operation or post operation (all P<0.05), and hypernatremia accounted for the highest proportion of the blood sodium abnormality.

In children with craniopharyngiomas, the imbalance of water and sodium exists before operation, and the incidence after operation seems significantly higher than that before operation. Hypernatremia is the main abnormal blood sodium in patients with CDI, IPTA and IPAA.

To explore the application value of magnetic resonance spectroscopy (MRS) in stereotactic biopsy for the diagnosis of glioma.

A retrospective analysis was conducted on the clinical data of 32 patients with glioma who were admitted to Department of Neurosurgery, the Sixth Medical Center of PLA General Hospital from June 2012 to December 2016. All patients underwent craniotomy to remove the tumor, and postoperative pathological examination verified the diagnosis of glioma. In this series, 14 cases underwent MRS-assisted stereotactic biopsy of tissues (experimental group) and 18 cases underwent regular MRI-assisted stereotactic biopsy without MRS (control group). Based on the pathological diagnosis determined post craniotomy, Fisher exact test was used to compare the accuracy of diagnosis of glioma between the 2 groups.

The differences in age, sex and imaging characteristics between the 2 groups were not statistically significant (all P >0.05). All 32 patients with glioma successfully underwent stereotactic biopsy, and none of the cases had intracranial hemorrhage, infection or new neurofunctional disorders post surgery. The ratio of accurate diagnosis in the experimental group was 13/14, which was higher than 10/18 in the control group, and the difference between the 2 groups was statistically significant ( P=0.044).

The application of MRS can obviously improve the accuracy of stereotactic biopsy for the diagnosis of glioma, which is instructive to the planning of surgical target of stereotactic biopsy.

To explore the experience of microneurosurgical technique to achieve bloodless excision of carotid body tumors (CBT).

The clinical data of 12 patients of CBT at Department of Neurosurgery, the First Affiliated Hospital of Soochow University from January 2016 to August 2019 were retrospectively analyzed in this study. Of the patients, 4 cases were males and 8 were females. All cases had unilateral (the left in 7 cases and the right in 5) lesion. The tumors were at least 4.2 cm × 3.0 cm × 3.0 cm, and at most 8.0 cm × 6.5 cm × 4.0 cm. Among the 12 patients, tumor blood supply was from external carotid artery and its branches in 9 cases, from carotid artery and internal carotid artery in 2 cases, and from vertebral artery in 1 case. According to the imaging Shamblin classification: 7 were classified as Shamblin type Ⅱ and 5 were type Ⅲ. One patient underwent selective tumor supplying artery (musculovertebral artery) embolization before surgery. All 12 patients underwent carotid body tumor resection under the microscope. Postoperative cranial CT and MRI were performed to observe whether there were hemorrhage, infarction and other complications, and carotid ultrasound was performed to check whether the vessels had occlusion or stenosis. Carotid ultrasound and CTA were followed up at outpatient clinic after discharge to evaluate whether there were tumor recurrence, vascular stenosis and stroke events.

Surgical excision was successfully performed in 12 cases. The operation duration was 95±25 min (60-180 min). One of the Shamblin Ⅲ patients had the rupture of carotid artery in two sites, suture hemostasis was employed, and the blood loss was 150 ml. The remaining 11 cases had intraoperative blood loss of 30±12 ml (20-50 ml). No intraoperative blood transfusion was applied. The pathological diagnosis of all 12 cases was paraganglioma. There were no perioperative deaths. Temporary hypoglossal nerve palsy occurred in 1 case. There was 1 case of slight stenosis at the suturing site of carotid artery indicated by CT reexamination. No complications such as cerebral infarction occurred in this series. All cases were followed up for 18±8 months (6-36 months). To the latest follow-up, there had been no tumor recurrence or cerebral infarction reported, and there was no death in this series. At 6 months post operation, the tongue deflection and dysphagia symptom were relieved in 1 patient with temporary hypoglossal nerve injury.

Microneurosurgical technology could be applied. After blocking the main blood supply of CBT, dissecting along the carotid artery adventitial-tumor capsule interface in a clear bloodless operative visual field, protecting the peripheral nerves, and maximizing the removal of tumors can achieve safe and bloodless removal of CBT.

To compare the efficacy of percutaneous trigeminal ganglion balloon compression (PBC) in the treatment of trigeminal neuralgia (TN) with different localization assistance techniques, and to explore the learning curve of Hartel technique.

The clinical data of 60 patients of idiopathic TN admitted to Neurosurgery Department of Lanzhou University First Hospital and 40 patients admitted to Neurosurgery Department of Characteristic Medical Center of Chinese People′s Armed Police Force from April 2016 to April 2019 were retrospectively analyzed. We conducted three stages of surgical training for 3 neurosurgeons. In the first stage, 20 patients were treated with Hartel puncture method (Hartel puncture group), 20 with stereotaxy assisted puncture method (stereotactic group) and 20 with neuronavigation assisted puncture method (neuronavigation group). The Hartel puncture method was applied in the second and third stages and 20 patients were treated during the time period. We then compared the efficacy of 3 different puncture methods in the first stage, compared the surgical efficacy of Hartel puncture method in the 3 stages, and drew the learning curve of Hartel puncture according to the operation time and number of procedures. The evaluation indexes of surgical efficacy included number of punctures, operation time, operation efficiency, incidence of complications of hospital stay and hospitalization cost.

For the first stage, there was no significant difference in gender, age, course of disease, operation time, operation efficiency or length of hospital stay among 3 groups (all P>0.05), while the number of surgical punctures, incidence of postoperative complications and hospitalization costs were statistically different (allP<0.05). The Hartel puncture group had the most punctures and highest postoperative complication rate, while the hospitalization cost was the least. There was no statistically significant difference in the gender, age, course of disease, surgical efficiency or hospitalization costs in the Hartel puncture training at three stages (allP>0.05), while as the training phase increased, the number of surgical punctures became less and less. The operation time became increasingly shorter, the operation efficiency was increasingly higher, the incidence of postoperative complications was increasingly lower, and the length of hospital stay was increasingly shorter (allP<0.05). By drawing the learning curve of Hartel′s puncture method, we found that after the number of surgical cases reached 40, the surgeon′s operation level gradually reached stability.

For beginners, stereotaxy and neuronavigation assisted methods are used in puncture of the foramen ovale, which could significantly reduce the incidence of postoperative complications while the medical cost would increase. After completing 40 cases of Hartel procedures, the operation level can be stabilized.

To explore the roles of PR domain zinc finger protein 2 (PRDM2) and c-Myc in the tumorigenesis and development of somatotroph adenomas at the tissue and cellular levels.

Seventy somatotroph adenomas specimens were obtained from patients with somatotroph adenomas who underwent tumor resection at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from July 2013 to December 2016. Three normal pituitary gland specimens were from donators of cadaver. The protein levels of PRDM2 and c-Myc were measured by immunochemistry. We further explored the relationship between PRDM2 and c-Myc protein levels in tumor tissue, as well as the relationship between PRDM2 and c-Myc proteins and tumor invasion and tumor volume. Somatotroph adenomas cell line GH3 cells were cultured in vitro and further divided into control group(blank cells), vector group(transfected with vectors only) and PRDM2 group (transfected with PRDM2 plasmid). Effect of PRDM2 on cell viability was detected by cell proliferation experiment, effect of PRDM2 on apoptosis was observed by flow cytometry, effect of PRDM2 on cell invasion ability was observed in the Transwell chamber experiment, and the effect of PRDM2 on the expression level of c-Myc in GH3 cells was detected by Western blot experiment.

According to the median immunohistochemistry score of 70 tumor specimens (PRDM2: 40, c-Myc: 170), the PRDM2 low-score group (<40) had a higher chance of invasion (19/35vs. 9/35, P=0.015) and larger tumor volume (17.8±4.5 cm³vs. 5.2±0.9 cm³, P<0.01) than the PRDM2 high-score group (≥40). The c-Myc high-score group (≥170) had a higher chance of invasion (20/35vs. 8/35, P=0.003) and larger tumor volume (15.5±3.5 cm³vs. 6.6±2.0 cm³, P=0.027) than the c-Myc low-score group (<170). PRDM2 and c-Myc levels in 70 tumor specimens were negatively correlated (r=-0.407, P=0.004). After 24 hours, 48 hours and 72 hours of GH3 cell transfection, the cell vitality of PRDM2 group was (82.2±6.3)%, (68.5±5.2)% and (54.7±3.6)% of that of control group respectively (all P<0.05), and the difference between the vector group and control group was not statistically significant (allP>0.05). The flow cytometry results showed that the ratios of Annexin Ⅴ positive cells and PI positive cells were (14.66±3.72)% and (6.21±2.17)% in PRDM2 group respectively, which were higher than those in control group [(3.35±1.03)% and (1.34±0.48)%, respectively, bothP<0.05]. The differences in the ratios of Annexin Ⅴ-positive cells and PI-positive cells between the vector group and control group were not statistically significant (bothP>0.05). The results of Transwell chamber experiment showed that the number of transmembrane positive cells in PRDM2 group was 145±37, which was lower than that of control group (415±76) (P<0.01). The Western blot experiment showed that the c-Myc level in the PRDM2 group was 0.32±0.12 folds of that in control group at 72 hours post transfection (P<0.01).

PRDM2 and c-Myc are both involved in the tumorigenesis of somatotroph adenomas, and PRDM2 could decrease the c-Myc level and inhibit the proliferation and invasion of GH3 cell line.