Stereotactically intracerebral transplantation of neural stem cells for ischemic stroke attenuated inflammatory responses and promoted neurogenesis: an experimental study with monkeys.

BACKGROUND: Ischemic stroke is a common neurovascular disorder with high morbidity and mortality. However, the underlying mechanism of stereotactically intracerebral transplantation of human neural stem cell (hNSC) is not well elucidated. MATERIALS AND METHODS: Four days after ischemic stroke induced by Rose Bengal photo-thrombosis, 7 cynomolgus monkeys were transplanted with hNSCs or vehicles stereotactically and followed up for 84 days. Behavioral assessments, magnetic resonance imaging, blood tests, and pathological analysis were performed before and after treatment. The proteome profiles of the left and right precentral gyrus and hippocampus were evaluated. Extracellular vesicle micro-RNA (miRNA) from the peripheral blood was extracted and analyzed. RESULTS: hNSC transplantation reduced the remaining infarcted lesion volume of cynomolgus monkeys with ischemic stroke without remarkable side effects. Proteomic analyses indicated that hNSC transplantation promoted GABAergic and glutamatergic neurogenesis, and restored the mitochondrial electron transport chain function in the ischemic infarcted left precentral gyrus or hippocampus. Immunohistochemical staining and qRT-PCT confirmed the promoting effects on neurogenesis and revealed that hNSCs attenuated post-infarct inflammatory responses by suppressing resident glia activation and mediating peripheral immune cell infiltration. Consistently, miRNA-sequencing revealed the miRNAs which were related to these pathways were down-regulated after hNSC transplantation. CONCLUSIONS: This study indicates that hNSCs can be effectively and safely used to treat ischemic stroke by promoting neurogenesis, regulating post-infarct inflammatory responses, and restoring mitochondrial function in both the infarct region and hippocampus.

Pairwise machine learning-based automatic diagnostic platform utilizing CT images and clinical information for predicting radiotherapy locoregional recurrence in elderly esophageal cancer patients.

OBJECTIVE: To investigate the feasibility and accuracy of predicting locoregional recurrence (LR) in elderly patients with esophageal squamous cell cancer (ESCC) who underwent radical radiotherapy using a pairwise machine learning algorithm. METHODS: The 130 datasets enrolled were randomly divided into a training set and a testing set in a 7:3 ratio. Clinical factors were included and radiomics features were extracted from pretreatment CT scans using pyradiomics-based software, and a pairwise naive Bayes (NB) model was developed. The performance of the model was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). To facilitate practical application, we attempted to construct an automated esophageal cancer diagnosis system based on trained models. RESULTS: To the follow-up date, 64 patients (49.23%) had experienced LR. Ten radiomics features and two clinical factors were selected for modeling. The model demonstrated good prediction performance, with area under the ROC curve of 0.903 (0.829-0.958) for the training cohort and 0.944 (0.849-1.000) for the testing cohort. The corresponding accuracies were 0.852 and 0.914, respectively. Calibration curves showed good agreement, and DCA curve confirmed the clinical validity of the model. The model accurately predicted LR in elderly patients, with a positive predictive value of 85.71% for the testing cohort. CONCLUSIONS: The pairwise NB model, based on pre-treatment enhanced chest CT-based radiomics and clinical factors, can accurately predict LR in elderly patients with ESCC. The esophageal cancer automated diagnostic system embedded with the pairwise NB model holds significant potential for application in clinical practice.

Concurrent mutations of germline GPR101 and somatic USP8 in a pediatric giant pituitary ACTH adenoma: a case report.

BACKGROUND: Cushing's disease (CD) is rare in pediatric patients. It is characterized by elevated plasma adrenocorticotropic hormone (ACTH) from pituitary adenomas, with damage to multiple systems and development. In recent years, genetic studies have shed light on the etiology and several mutations have been identified in patients with CD. CASE PRESENTATION: A girl presented at the age of 10 years and 9 months with facial plethora, hirsutism and acne. Her vision and eye movements were impaired. A quick weight gain and slow growth were also observed. Physical examination revealed central obesity, moon face, buffalo hump, supra-clavicular fat pads and bruising. Her plasma ACTH level ranged between 118 and 151 pg/ml, and sella enhanced MRI showed a giant pituitary tumor of 51.8 × 29.3 × 14.0 mm. Transsphenoidal pituitary debulk adenomectomy was performed and immunohistochemical staining confirmed an ACTH-secreting adenoma. Genetic analysis identified a novel germline GPR101 (p.G169R) and a somatic USP8 (p. S719del) mutation. They were hypothesized to impact tumor growth and function, respectively. CONCLUSIONS: We reported a rare case of pediatric giant pituitary ACTH adenoma and pointed out that unusual concurrent mutations might contribute to its early onset and large volume.

Atorvastatin combined with dexamethasone in chronic subdural haematoma (ATOCH II): study protocol for a randomized controlled trial.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH. METHODS: The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days. DISCUSSION: This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH. TRIAL REGISTRATION: ChiCTR, ChiCTR1900021659 . Registered on 3 March 2019, http://www.chictr.org.cn/showproj.aspx?proj=36157 .

Correlation analysis between short-term insulin-like growth factor-I and glucose intolerance status after transsphenoidal adenomectomy in acromegalic patients: a large retrospective study from a single center in China

ABSTRACT Objectives: Our study aimed to investigate the associations of glucose tolerance status with insulin-like growth factor-I (IGF-I) and other clinical laboratory parameters of acromegalic patients before and after the patients underwent transsphenoidal adenomectomy (TSA) by conducting a single-center, retrospective study. Subjects and methods: A total of 218 patients with acromegaly who had undergone TSA as the first treatment were retrospectively analyzed. Serum IGF-I, growth hormone (GH) and glucose levels were measured before and after surgery. Results: The follow-up levels for random GH, GH nadir, and the percentage of the upper limit of normal IGF-I (%ULN IGF-I) were decreased significantly. The percentages of normal (39.0%), early carbohydrate metabolism disorders (33.0%) and diabetes mellitus (28.0%) changed to 70.2%, 16.5% and 13.3%, respectively, after TSA. %ULN IGF-I at baseline was higher in the diabetes mellitus (DM) group than in the normal glucose tolerance group and impaired glucose tolerance (IGT) /impaired fasting glucose (IFG) groups before TSA, and the DM group exhibited a greater reduction in %ULN IGF-I value after surgery. The follow-up %ULN IGF-I value after surgery was significantly lower in the improved group, and Pearson's correlation analysis revealed that the reductions in %ULN IGF-I corresponded with the reductions in glucose level. Conclusion: This study examined the largest reported sample with complete preoperative and follow-up data. The results suggest that the age- and sex-adjusted IGF-I level, which reflects altered glucose metabolism, and the change of it are associated with improved glucose tolerance in acromegalic patients both before and after TSA.

Correlation analysis between short-term insulin-like growth factor-I and glucose intolerance status after transsphenoidal adenomectomy in acromegalic patients: a large retrospective study from a single center in China.

OBJECTIVES: Our study aimed to investigate the associations of glucose tolerance status with insulin-like growth factor-I (IGF-I) and other clinical laboratory parameters of acromegalic patients before and after the patients underwent transsphenoidal adenomectomy (TSA) by conducting a single-center, retrospective study. SUBJECTS AND METHODS: A total of 218 patients with acromegaly who had undergone TSA as the first treatment were retrospectively analyzed. Serum IGF-I, growth hormone (GH) and glucose levels were measured before and after surgery. RESULTS: The follow-up levels for random GH, GH nadir, and the percentage of the upper limit of normal IGF-I (%ULN IGF-I) were decreased significantly. The percentages of normal (39.0%), early carbohydrate metabolism disorders (33.0%) and diabetes mellitus (28.0%) changed to 70.2%, 16.5% and 13.3%, respectively, after TSA. %ULN IGF-I at baseline was higher in the diabetes mellitus (DM) group than in the normal glucose tolerance group and impaired glucose tolerance (IGT) /impaired fasting glucose (IFG) groups before TSA, and the DM group exhibited a greater reduction in %ULN IGF-I value after surgery. The follow-up %ULN IGF-I value after surgery was significantly lower in the improved group, and Pearson's correlation analysis revealed that the reductions in %ULN IGF-I corresponded with the reductions in glucose level. CONCLUSION: This study examined the largest reported sample with complete preoperative and follow-up data. The results suggest that the age- and sex-adjusted IGF-I level, which reflects altered glucose metabolism, and the change of it are associated with improved glucose tolerance in acromegalic patients both before and after TSA.

[Influence of Nasal Disinfection on Nasal Bacterial Colonization through the Transsphenoidal Approach].

Objective To explore the influence of the iodine disinfection on nasal bacterial colonization through the transsphenoidal approach. Methods Totally 133 pituitary adenoma patients who underwent transsphenoidal surgery in our department from January to August 2017 were enrolled in this study. Before disinfection,pharyngeal swabs of inferior turbinate root secretions were taken for bacterial culture. After iodine disinfection,pharyngeal swabs were taken again at the same site. Changes in the nasal bacterial spectrum before and after disinfection were compared. Patients were followed up for three months after the surgery,during which any intracranial infection/bacteraemia was recorded,and its correlation with nasal bacteria colonization was analyzed. Results Nasal bacterial colonization was detected in 45 (33.8%) of 133 patients before iodine disinfection and in only 6 cases (4.5%) after iodine disinfection (χ2=34.5,P=0.000). Thus,iodine disinfection eliminated 86.7%(39/45) of the colonized bacteria. The most common nasal bacterium was Staphylococcus aureus (24.4%,11/45),followed by Klebsiella pneumoniae (24.4%,11/45),and Staphylococcus epidermidis (13.3%,6/45). One patient had high fever and chills 2 days after surgery,but blood culture and cerebrospinal fluid culture showed negative Results . After the administration of third-generation cephalosporins,the symptoms disappeared after two days. Conclusion sThere are colonized bacteria in nasal cavity. Iodine disinfection of nasal cavity can effectively clear most of the nasal bacteria. The possibility of intracranial infection/bacteremia after transsphenoidal approach is low.

Surgical treatment for male prolactinoma: A retrospective study of 184 cases.

A total of 184 cases of surgically treated male prolactinoma were analyzed retrospectively to summarize the outcome of this surgical intervention. We analyzed the general characteristics, clinical manifestations, hormone levels, imaging features, preoperative treatments, surgical outcomes, pathology results, and follow-up records for all included patients. The most common clinical manifestations included sexual dysfunction (47.4%), headache (55.9%), and visual disturbance (46.7%). Serum prolactin levels ranged from 150 to 204,952 ng/mL. Tumor size varied from 6 to 70 mm. Pituitary adenomas grew in a parasellar pattern with visual deficits occurring 40.7% of the time. After surgical therapy, 88.6% of patients achieved symptom relief, and 98.4% experienced an immediate postoperative decline in prolactin level. Fifty-seven patients (31.0%) achieved initial remission, and 26 patients (45.6%) experienced recurrence. Hence, our results suggest that in male prolactinoma characterized by a large pituitary diameter and high serum prolactin level, tumor size predicts the degree of gross resection. The prognostic predictors included preoperative tumor growth pattern and Ki-67 index.Citation: Yi-jun S, Mei-ting C, Wei L, Bing X, Yong Y, Ming F, Ren-zhi W. (2016) Surgical treatment for male prolactinoma: a retrospective study of 184 cases.

Intraparenchymal endodermal cyst with spontaneous intracystic hemorrhage in the temporal lobe of an adult.

BACKGROUND: Endodermal cysts (EC) are rare but well-known congenial lesions of the central nervous system mainly located in the spinal subdural space. Intracranial ECs are rare and commonly encountered in the posterior cranial fossa as extra-axial lesions; an intraparenchymal location is exceedingly rare. A complete removal is the best surgical strategy and any residue can cause recurrence. It is necessary to exclude EC in patients with intracranial cystic lesions. We present a case of intraparenchymal EC with spontaneous intracystic hemorrhage in the temporal lobe of an adult. METHODS: A 43-year-old man presented with headache and memory deterioration. Brain computed tomography and magnetic resonance imaging showed a slightly enhanced temporal lobe cystic lesion, which was homogenously hyperintense on T1-and T2-weighted images. There was a suspicion of brain abscess at admission. The lesion was totally removed with a left subtemporal craniotomy. Histological examination revealed an EC with intracystic hemorrhage. RESULTS: The preoperative symptoms were relieved after surgery and 3-month follow-up magnetic resonance imaging found no cystic signs. CONCLUSION: This case suggests that EC should be considered in the differential diagnosis of intracranial cystic lesions and a complete removal is the best strategy of choice.

Predictive Factor of Surgical Efficacy in Male Patients with Prolactinoma.

Objective To analyze the predictive factor of surgical efficacy in male patients with prolactinoma. Method The clinical data of 184 male patients with prolactinoma who had undergone surgery were retrospectively analyzed.Results Before the surgery,the serum prolactin level from 150 to 204 952 ng/ml,the tumors sized 6 to 70 mm. Macroadenoma was seen in 152 cases (82.6%) and suprasellar adenoma with visual deficitsin 75 cases (40.7%). Complete resection was achieved in 149 patients. After surgical therapy,postoperative immediate prolactin level declined in 182 patients (98.4%);57 patients (31.0%)achieved initial remission,while the disease recurred in 26 patients (45.6%).Larger tumor had significantly lower rate of complete resection (P<0.05). The recurrence rate was significantly higher in the group with higher Ki-67 index (P<0.001). The recurrence rate was significantly lower in patients with intrasellar adenoma (P<0.001).No significant relationship was found between preoperative prolactin level and complete resection (P=0.306). Conclusions Tumor size can predictthe degree of surgical resection. The prognostic factors include tumor size,preoperative growth pattern of prolactinoma,and Ki-67 index.

Curative effects of head γ-SRT for the treatment of functional pituitary macroadenoma.

The aim of the study was to examine the curative effects and proper radiotherapy plan of head γ-stereotactic radiotherapy (γ-SRT) for the treatment of functional pituitary macroadenoma. Clinical samples of 30 patients that underwent γ-SRT (radiotherapy group) and 26 patients that underwent pituitary adenoma resection via single nasal-sphenoidal approach (surgery group) were analyzed retrospectively and their curative effects were compared. The results showed that in the radiotherapy group, 12 cases accepted single fraction irradiation, with an average maximum diameter of tumor body of 1.8±0.6 cm, average volume of 0.6±0.4 cm3, average dose of the central point of 52.6±18.7 Gy, average dose of the peripheral point of 24.7±10.2 mGy, and isodose curve of 50-70%. The remaining 18 cases accepted multiple fraction irradiation, with an average irradiation of 3.7±1.6 times, maximum average diameter of tumor body of 4.3±1.8 cm, average volume of 4.8±2.7 cm3, average dose of the central point of 24.6±12.5 Gy, average dose of the peripheral point of 13.6±7.4 mGy, and isodose curve of 50-70%. Following treatment, the tumor volumes of patients in the radiotherapy group that received single and multiple irradiation were significantly reduced and the visual acuity and visual field were improved (p<0.05). The two groups were followed up for an average of 3.8 years, and the follow-up results showed that differences of the two groups on the tumor control, mortality and hypopituitarism rates were not statistically significant (p>0.05). In addition, the incidence of complications of the radiotherapy group was significantly decreased as compared to that of the surgery group (p<0.05). In conclusion, γ-SRT was safe and effective for the treatment of functional pituitary adenomas. Its curative effects were equivalent to that of the microscopic single nasal-sphenoidal approach with fewer complications.

Protection of Nerve Injury with Exosome Extracted from Mesenchymal Stem Cell.

OBJECTIVE: To investigate the protective effect of Exosomes from human adipose-derived mesenchymal stem cells (hAMSCs) in neural injury induced by glutamate and its possible mechanism. METHODS: Characteristics of Exosomes from hAMSCs were identified by electron microscopy and Western blot analysis. Cytokines that might play a major role in the protective effect were tested by enzyme-linked immunosorbent assay (ELISA). The protective action of Exosome and its possible signaling pathway were researched by the in vitro neural injury induced by glutamate, including control group (without Glu), Glu group (dealing with Glu), Glu+Exo group (dealing with Glu +100 ng/ml Exo), Glu+Exo+Akt group (dealing with Glu+100 ng/ml Exo+10 µmol/L Akt), Glu+Exo+Erk group (dealing with 100 ng/ml Glu+100 ng/ml Exo+10 µmol/L Erk), and Glu+Exo+TrkB group (dealing with Glu+100 ng/ml Exo +10 µmol/L TrkB). RESULTS: Exosomes from hAMSCs had similar sizes to those isolated from other kinds of cells, and expressed the characteristic proteins such as CD63, CD81, HSP70, and HSP90. Cytokines that had neurotrophic effects on Exosomes were mainly insulin-like growth factor and hepatocyte growth factor, with the concentration being 9336.49±258.63 and 58,645.50±16,014.62, respectively; brain derived neurotrophic factor, nerve growth factor,and vascular endothelial growth factor had lower levels, with the concentration being 1928.25±385.47, 1136.94±5.99, and 33.34±9.43, respectively. MTS assay showed that the PC12 cell survival rates were 0.842±0.047, 0.306±0.024, 0.566±0.026, 0.461±0.016, 0.497±0.003, and 0.515±0.034 in the control group, Glu group, Glu+Exo group, Glu+Exo+Akt group, Glu+Exo+Erk group, and Glu+Exo+TrkB group; obviously, it was significantly lower in Glu group than in control group (P=0.02), significantly higher in Glu+Exo group than in Glu group (P=0.01), and significantly lower in Glu+Exo+Akt group than in Glu+Exo group (P=0.01). CONCLUSION: Exosomes secreted from hAMSCs have protective effect against neuron damage induced by glutamate, which may be mediated through activating the PI3/K-Akt signalling pathway.

Effect of Transsphenoidal Adenectomy on Glucose Tolerance Status in Patients with Growth Hormone-secreting Pituitary Adenoma.

OBJECTIVE: To explore the effect of transsphenoidal adenectomy on glucose tolerance status in patients with growth hormone (GH)-secreting pituitary adenoma. METHODS: The clinical data of 105 patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenectomy in our department in 2013 were retrospectively analyzed. The glucose tolerance status, GH level, and insulin-like growth factor-1 (IGF-1) level before and after surgery were compared. RESULTS: Among these 105 patients, the blood glucose tolerance status included normal glucose tolerance (NGT) in 47 cases (44.8%), early carbohydrate metabolism disorders (ECMDs) in 26 cases (24.8%), and diabetes mellitus (DM) in 32 cases (30.5%) before surgery. After the surgery, the fasting blood glucose (P=0.006, P=0.017) and postprandial blood glucose (P=0.000, P=0.000) in the ECMDs and DM groups were significantly improved. Also, the random GH (P=0.001, P=0.004, P=0.001), nadir GH (P=0.000, P=0.001, P=0.001), and IGF-1 (P=0.005, P=0.000, P=0.000) significantly decreased during the follow-up period in NGT, ECMDs and DM groups. Compared with ECMDs and DM groups, the decrease in fasting blood glucose (P=0.029, P=0.000), postprandial blood glucose (P=0.003, P=0.000), and serum IGF-1 (P=0.048, P=0.000) were more significant in DM group. CONCLUSIONS: Transsphenoidal adenectomy can improve the blood glucose, GH, and IGF-1 levels in patients with growth hormone-secreting pituitary adenoma. Meanwhile,the surgery has a better effect in improving the glucose tolerance status and IGF-1 in patients with preoperatively confirmed DM.

Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host Microenvironment.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD.