Objective:To assess the prognostic value of cerebrospinal fluid (CSF) neuron specific enolase (NSE) combined with protein content in predicting poor prognosis in patients with intraventricular hemorrhage after external ventricular drainage (EVD).Methods:The clinical data of 73 intraventricular hemorrhage patients underwent EVD in the Second Affiliated Hospital of Wenzhou Medical University from February 2019 to January 2022 were retrospectively analyzed. After 90 d of surgery, 37 patients (good prognosis group) had a modified Rankin score of 0 to 2, while 36 cases (poor prognosis group) had a score of 3 to 5. The baseline characteristics including gender, age, hypertension, diabetes and Glasgow coma score (GCS) upon admission were recorded. The peripheral blood samples were collected within 24 h of admission to measure C-reactive protein, white blood cell and blood potassium. The CSF samples were obtained within 24 h after EVD to measure NSE, protein content, white blood cell and red blood cell. Binary Logistic regression analysis was used to analyze the independent risk factors of poor prognosis in patients with intraventricular hemorrhage after EVD. The efficacy of CSF NSE combined with protein content in predicting the poor prognosis in patients with intraventricular hemorrhage after EVD was evaluated by the receiver operating characteristics (ROC) curve.Results:There were no statistical differences in gender distribution, age, hypertension, diabetes, blood C-reactive protein, white blood cell and blood potassium between two groups ( P>0.05); the GCS upon admission in poor prognosis group was significantly lower than that in good prognosis group: (5.83 ± 0.20) scores vs. (9.54 ± 0.43) scores, the CSF NSE, protein content, white blood cell and red blood cell were significantly higher than those in good prognosis group: (377.94 ± 21.91) μg/L vs. (86.43 ± 11.96) μg/L, (16.70 ± 2.07) g/L vs. (2.92 ± 0.74) g/L, (731.61 ± 141.36) × 10 6/L vs. (302.16 ± 90.99) × 10 6/L and (410 332 ± 88 584) × 10 6/L vs. (156 075 ± 61 387) × 10 6/L, and there were statistical differences ( P<0.01 or <0.05). Binary Logistic regression analysis result showed that elevated CFS NSE and higher CSF protein content were independent risk factors of poor prognosis in patients with intraventricular hemorrhage after EVD ( OR = 1.053 and 1.270, 95% CI 1.005 to 1.103 and 1.020 to 1.581, P<0.05). ROC curve analysis result showed that the area under the curve of CFS NSE combined with protein content detection to predict the poor prognosis in patients with intraventricular hemorrhage after EVD was larger than that of CFS NSE and protein content alone detection (0.982 vs. 0.971 and 0.903), and the optimal cutoff values of CSF NSE and protein content were 233.090 μg/L and 1.425 g/L, respectively. Conclusions:CSF NSE and protein content are significantly elevated in patients with intraventricular hemorrhage after EVD. The combined detection of CSF NSE and protein content provides valuable prognostic information for prognosis in patients with intraventricular hemorrhage after EVD, and it can provide important basis for prognosis evaluation.

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.
Animals ; Mice ; Corticotropin-Releasing Hormone/metabolism* ; Nucleus Accumbens/metabolism* ; Receptors, Corticotropin-Releasing Hormone/metabolism* ; Sleep ; Sleep Wake Disorders ; Stress, Psychological/complications*

Objective:To explore the therapeutic effect of anti-interleukin (IL)-12/IL-23 p40 antibody on experimental autoimmune uveitis (EAU) and its mechanism.Methods:Sixty-six SPF female C57BL/6N mice aged 6-8 weeks were selected.EAU model was established in 24 mice through immunization with the interphotoreceptor retinoid-binding protein (IRBP) 651-670.The 24 mice were sacrificed before immunization, and on the 3rd, 12th, and 18th day after immunization, with 6 at each time point.Flow cytometry was used to detect the proportion of IL-17A + interferon-γ (IFN-γ) + CD4 + T cells in the spleen, lymph nodes and eyeballs.Another 6 mice were selected to establish EAU model, and fundus images of the mice were taken with a small animal imaging instrument and optical coherence tomography (OCT) 18 days after immunization.The 6 mice were sacrificed after OCT examination and the eyeballs were collected.Hematoxylin-eosin staining was used to observe the retinal inflammation and morphological changes in tissue structure.Flow cytometry was employed to detect the proportion of IL-17A + IFN-γ + CD4 + T cells in lymph nodes.The 6 mice were divided into IL-17A + IFN-γ + highly expressed group and IL-17A + IFN-γ + lowly expressed group according to flow cytometry results, and the retinal injury was compared between the two groups.EAU model was established in another 36 mice, which were divided into anti-IL-12/IL-23 p40 group and IgG group by random number table method, with 18 mice in each group.Anti-IL-12/IL-23 p40 or IgG was injected by tail vein at a 3-day inteval according to grouping.On the 12th and 18th day after immunization, 6 mice were selected from each group to collect lymph nodes and eyeballs, and the proportion of T cell subsets was detected by flow cytometry.Eyeballs of 6 mice in each group were extracted on the 24th day after immunization and retinal damage was observed by hematoxylin-eosin staining.The induced differentiation of CD4 + T cells in vitro was assayed by flow cytometry.The expressions of IL-17 and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA) after induced differentiation of IL-17A + IFN-γ + CD4 + T cells.The relative expression levels of Th1 transcription factor T-bet and Th17 transcription factor retinoid acid-related orphan nuclear receptor γt (ROR-γt) after induced differentiation of IL-17A + IFN-γ + CD4 + T cells were detected by real-time quantitative PCR.The use and care of animals followed the ARVO statement and this study protocol was approved by an Ethics Committee of Experimental Animals of Tianjin Medical University Eye Hospital (No.TJYY2019111019). Results:There were significant differences in the proportion of IL-17A + IFN-γ + CD4 + T cells in lymph nodes, spleen and eyeballs between wild-type mice and EAU mice at the 3rd, 12th and 18th day after immunization ( H=9.642, 16.531, 10.385; all at P<0.05). Compared with before immunization, the proportion of IL-17A + IFN-γ + CD4 + T cells was significantly increased in lymph nodes of EAU mice on the 12th day following immunization and was significantly increased in spleen and lymph nodes on day 18 after immunization (all at P<0.05). Severe retinal exudation, retinal detachment, severe inflammatory cell infiltration and extensive retinal folds were detected in IL-17A + IFN-γ + highly expressed mice.Mild retinal edema, focal inflammatory cell infiltration and mild retinal folds were found in IL-17A + IFN-γ + lowly expressed mice.The proportion of CD3 and IL-17A + IFN-γ + CD4 + T cells in the eyeballs of anti-IL-12/IL-23 p40 group was lower than that in IgG group at the 18th day after immunization, and the differences were statistically significant ( t=15.304, 8.080; both at P<0.05). On day 12 after immunization, the percentage of IL-17A + IFN-γ + CD4 + T cells in anti-IL-12/IL-23 p40 group was (0.33±0.18)%, which was significantly lower than (4.83±0.45)% in IgG group ( t=15.974, P<0.001). Compared with IgG group, the percentage of Th1, Th17, IL-17A + IFN-γ + CD4 + T cells and the expression levels of IL-17, IFN-γ, T-bet, ROR-γt in anti-IL-12/IL-23 p40 group were significantly decreased, with statistical significances (all at P<0.05). Conclusions:Anti-IL-12/IL-23 p40 has a therapeutic effect on EAU by inhibiting IL-17A + IFN-γ + CD4 + T cells.

Objective To establish a blast injury experimental model using a shock tube at lateral lying position of C57BL/6 mice, investigate biomechanical responses of macrophages/microglia cells in the heart, lung and brain tissues to mechanical damage by shock wave within 24 hours. Methods Shock tube was employed to generate a shock wave to C57BL/6 mice. Firstly, the weight changes of mice were measured at different time points after the shock. Then the cardiac, pulmonary and whole brain tissue samples were dissected after anesthesia. Pathological sections were stained with HE staining to detect structural damage; the TUNEL staining method was used to mark and count the proportion of dead cells in each tissue. Microglial cells were labeled with fluorescent antibody, while responses and changes of macrophages/microglia after shock loading were analyzed. Results The shock tube exerted 179 kPa overpressure shock wave upon sideway of the mouse, and lethal rate of the mouse was 3.33%. Compared with normal control group, the mice in experimental group had a significant weight loss within 24 hours after loading shock. Pathological sections showed rupture of lung tissues after shock, accompanied by alveolar protein deposition, pulmonary bulla and other diseases. Fluorescence staining showed that lung tissue was recruited and activated in a large amount within 24 hours. The proportion of dead cells cleared rebounded to normal level within 24 hours. The heart was highly tolerant to shock, and macrophages appeared near the large blood vessels. The brain showed unilateral aggregation of microglia due to the impact posture, mainly due to prolonged inflammation and a higher proportion of dead cells at the junction of gray and white matter. Conclusions A blast shock model at lateral lying position of the mouse was established. Within 24 hours, macrophages/microglia were recruited quickly to the injury site after being impacted, which mediated strong immune stress, and might participate in the immune response to trigger a second long-term inflammatory injury. The results of the study provide experimental basis for the evaluation of primary impact injury, such as dose-effect relationship and tissue damage difference.

Objective:To investigate the efficacy of microsurgical treatment in cavernous sinus tumors.Methods:The clinical data of 87 patients with cavernous sinus tumor treated by microsurgery from January, 2010 to August, 2019 were analysed retrospectively. The surgical approaches and microsurgical skills for common tumors in Cavernous Sinus region were discussed. The follow-up included outpatient and telephone follow-ups, and the follow-up results were evaluated by KPS score.Results:Among the 87 cases, 57 were totally resected (65.5%), 14 were subtotal resected (16.1%) and 16 were major resected (18.4%). Hospitalisation ranged from 14 to 98 days, with an average of 29 days. Postoperative complications occurred in 30 cases with cranial nerve injury, 2 brain stem injury, 4 postoperative bleeding, 5 cerebrospinal fluid leakage, 4 infection, 1 Pituitary damage and 1 death. Prognosis and follow-up analysis showed 68 cases with KPS>60 and 66 with KPS>80 at 1 month after surgery; 74 with KPS>70 and 72 with KPS>80 at 3 months after surgery; 78 with KPS>80 by 12 months after surgery. During the follow-up period of 6-120 months, 3 cases died. Recurrence: 6 of incomplete resection of meningioma, were in 1-6 years after the surgery, 4 of incomplete resection of schwannoma in 1-8 years, 2 of pituitary adenoma respectively in 13 and 16 months after the surgery. There was no recurrence after reoperation. Two cases of chondrosarcoma, 3 of chordoma and 3 of germinoma were treated with radiotherapy, and during the follow-up, there was no progress of the focus. No tumor progression or recurrence was found in other cases during follow-up.Conclusion:Surgery of cavernous sinus tumor is difficult due to frequent postoperative complications. Reasonable preoperative plan, surgical approach and precise microsurgical techniques are the keys in reduction of postoperative complications and in the improvement of prognosis.

OBJECTIVE: To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics. METHODS: Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes. RESULTS: The expression level of miR-181b in CLL patients was significantly lower than that in control group (P＜0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P＜0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging. CONCLUSION The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.
Apoptosis Regulatory Proteins ; Cell Proliferation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; Prognosis

Objective To evaluate the value of CT plus CTA in emergency surgical treatment of spontaneous intracerebral hemorrhage caused by brain arteriovenous malformations(AVM). Methods A total of 15 cases diagnosed with spontaneous intracerebral hemorrhage by emergent CT examination in the Second Affiliated Hospital of Wenzhou Medical University were retrospectively reviewed from May 2015 to June 2018, and subsequent emergent CTA examination was adopted to verify whether the patients had brain AVM that was responsible for the hemorrhage. After diagnosis, emergency surgical resection of the brain AVM and evacuation of hematoma were performed. Glasgow outcome score (GOS) was used to evaluated the outcome. A secondary DSA or CTA was performed from 2 weeks to 6 months post the operation. Results All 15 cases exanimated by emergent CT plus CTA were demonstrated to have brain AVM and intracranial hematoma. All the patients received emergency brain AVM resection and hematoma evacuation. The surgical finding during operation was in line with what was seen on emergent CT plus CTA, and all cases got total hematoma evacuation. Twelve cases received total brain AVM resection, and the other 3 cases received partial resection because the residual AVM foci existed in deep brain structures . After the operation, none had rebleeding at the surgical site. Follow-up DSA or CTA confirmed the 12 cases had total resection and the other 3 cases had partial resection. All patients were alive after the surgery and GOS scores during the follow-up time, from 2 weeks to 6 months after emergency surgery, were: 5 in 6 patients, 4 in 4 patients, 3 in 4 patients and 2 in 1 patient. Conclusions CT plus CTA can better show the relationship between vascular malformation, hematoma, and the adjacent anatomical structure, and therefore may contribute to intraoperative judgment and complete resection of vascular malformation. It is a practical imaging tool for the preoperative evaluation and emergency surgical treatment of spontaneous intracerebral hemorrhage caused by brain AVM.

OBJECTIVE: Epidural haematoma (EDH) most commonly occurs in the supratentorial area, particularly in the temporal region, of the brain. Posterior fossa epidural haematoma (PFEDH) is less frequently observed, accounting for only 1.2% to 12.9% of all EDH cases. Because of the non-specific symptoms and the potential for rapid and fatal deterioration in children, an early computed tomography (CT) scanning is necessary for all suspicious cases. The aim of the present study was to share the experience of 48 cases and review the literature concerning PFEDH.METHODS: A retrospective analysis was conducted for 48 paediatric cases diagnosed with PFEDH and admitted to Yuying Children’s Hospital of Wenzhou Medical University from January 2010 to August 2015. The clinical features and outcomes were analyzed and compared with previous literature.RESULTS: Seventeen patients were surgically treated in this series and 31 patients received non-operative treatment. The outcomes were good in 46 patients, evaluated using the Glasgow outcome score (GOS), while mild disability was observed in one patient, and only one case showed severe disability. There were no cases of mortality in this series.CONCLUSION: Posterior fossa epidural haematoma is relatively rare compared with supratentorial epidural haematoma. Early and serial CT scans should be performed for all suspicious cases. The criteria for the surgical treatment of paediatric patients with PFEDH were concluded. The overall prognosis was excellent in paediatric patients.
Brain ; Child ; Hematoma ; Humans ; Mortality ; Prognosis ; Retrospective Studies ; Temporal Lobe ; Tomography, X-Ray Computed

Objective: To observe the expression of retinal proteins in experimental autoimmune uveitis (EAU) mice and to explore the possible molecular mechanism of autoimmune uveitis. Methods: Twelve female C57BL/6J mice were randomly divided into model group and normal control group, 6 mice in each group.In the model group, the EAU model was established by subcutaneous injection of human interphotoreceptor retinoid-binding protein (IRBP) 651-670.The fundal change of EAV mice was assessed by direct ophthalmoscope, OCT and histopathological staining.At 18 days after immunization, the retinas of the two groups were taken for retinal protein extraction, protein restriction enzyme digestion, mass spectrometry detection, data analysis, and bioinformatics analysis.This study was approved by the experimental animal Ethics Committee of Tianjin Medical University Eye Hospital (TJYY2018070113). The feeding and use of experimental animals follow the ARVO statement. Results: The EAU mouse model was successfully established.At 10 days after immunitation, the retina of EAV mouse was damaged.At 18 days after immunization, retinal edema and infiltration of inflammatory cells into vitreous were observed.Proteomic results showed that a total of 4 458 proteins were identified in this study, of which 522 were differentially-expressed proteins (fold change>1.5, P<0.05). Among these differentially-expressed proteins, 147 proteins including Stat1 and Stat3 were up-regulated and 375 proteins including Gucy2f and Rho were down-regulated.These differentially-expressed proteins were closely related to platelet activation, integrin signaling, T cell activation, the phototransduction cascade, Toll-like receptor and so on. Conclusions EAU is related to the abnormal expression of Stat1, Stat3 and other proteins, as well as the abnormal regulation of platelet activation and integrin signal pathway.

Objective:To evaluate the value of intraoperative magnetic resonance imaging (iMRI) combined with neuronavigation for the resection of insular gliomas.Methods:From August 2014 to October 2017 in the First Hospital Affiliated to Sun Yat-sen University,clinical data of 41 patients with insular glioma,who underwent the surgery assisted with 3.0T iMRI and neuronavigation,were analyzed retrospectively,and the resection extent,complications and prognosis were evaluated.Results:Subtotal tumor resection was achieved in 21 patients and partial resection was done in 20 after iMRI scanning.After further resection,total tumor resection was achieved in 16 patients,subtotal resection in 18 and partial resection in 7.There was a statistical significant difference in tumor resection between pre-iMRI and post-iMRI according to the Fisher test (P＜0.05).In the follow-up from 3 months to 3 years,the symptoms of the 41 patients had improved.Conclusion:iMRI corrected the shift of brain.Neuronavigation can accurately and timely assess the degree of resecting tumor.The combination of neuronavigation with surgery can maximally and safely resect insular glioma.