The Rejuvenation and Functional Restoration of Aged Adipose Stem Cells by DUXAP10 Knockdown via the Regulation of the miR-214-3p/RASSF5 Axis.

Adipose stem cell (ASC)-based therapies provide an encouraging option for tissue repair and regeneration. However, the function of these cells declines with aging, which limits their clinical transformation. Recent studies have outlined the involvement of long non-coding RNAs in stem cell aging. Here, we reanalyzed our published RNA sequencing (RNA-seq) data profiling differences between ASCs from young and old donors and identified a lncRNA named double homeobox A pseudogene 10 (DUXAP10) as significantly accumulated in aged ASCs. Knocking down DUXAP10 promoted stem cell proliferation and migration and halted cell senescence and the secretion of proinflammatory cytokines. In addition, DUXAP10 was located in the cytoplasm and functioned as a decoy for miR-214-3p. miR-214-3p was downregulated in aged ASCs, and its overexpression rejuvenated aged ASCs and reversed the harm caused by DUXAP10. Furthermore, Ras Association Domain Family Member 5 (RASSF5) was the target of miR-214-3p and was upregulated in aged ASCs. Overexpressing DUXAP10 and inhibiting miR-214-3p both enhanced RASSF5 content in ASCs, while DUXAP10 knockdown promoted the therapeutic ability of aged ASCs for skin wound healing. Overall, this study offers new insights into the mechanism of age-related ASC dysfunction and names DUXAP10 and miR-214-3p as potential targets for energizing aged stem cells.

Deciphering the role of extrachromosomal circular DNA in adipose stem cells from old and young donors.

BACKGROUND: The functional impairment of adipose stem cells (ASCs) during aging limits their clinical transformation. Studies have shown that extrachromosomal circular DNAs (eccDNAs) are associated with tumor progression and cell aging, but the roles of eccDNAs in ASCs remain unknown. METHOD: We conducted Circle sequencing (Circle-seq) to identify eccDNAs in ASCs isolated from young and old donors. The differentially expressed eccDNAs were calculated, annotated and validated via polymerase chain reaction. RESULTS: Thousands of eccDNAs were identified and comprehensively characterized. Most of them were GC-rich, < 1000 base pairs in size, and were enriched on chromosome 19 and 17 with a high density of Alu elements and genes, 2 kb upstream/downstream of genes and satellites. In total, 3025 eccDNAs were differentially expressed among the two ASC groups. Conjoint analysis of the Circle-seq results and previous RNA-seq results revealed that 73 eccDNAs and 55 genes exhibited the same differential expression between the two groups. KEGG and GO analyses revealed that genes encoding differentially expressed eccDNAs were enriched for cell adhesion, cellular senescence and TGF-ß receptor signaling pathway. We also found that aged ASCs exhibited loss of eccDNAs, including CAMK2G (chr10: 75577899-75578176), TRABD2B (chr1: 48305638-48307008) and TRABD2B (chr1: 48305425-48307091). CONCLUSION: In this study, we elucidated the first eccDNA profile relating to ASCs and demonstrated that three eccDNAs are lost in aged ASCs, which may be potential biomarkers of stem cell aging and valuable targets for stem cell rejuvenation.

Visualization balloon occlusion-assisted technique in the treatment of large or giant paraclinoid aneurysms: A study of 17 cases series.

Objective: Although balloon-assisted techniques are valuable in aneurysm clipping, repeated angiography and fluoroscopy are required to understand the location and shape of the balloon. This study investigated the value of visualization balloon occlusion-assisted techniques in aneurysm hybridization procedures. Methods: We propose a visualization balloon technique that injects methylene blue into the balloon, allowing it to be well visualized under a microscope without repeated angiography. This study retrospects the medical records of 17 large or giant paraclinoid aneurysms treated by a visualization balloon occlusion-assisted technique in a hybrid operating room. Intraoperative surgical techniques, postoperative complications, and immediate and long-term angiographic findings are highlighted. Results: All 17 patients had safe and successful aneurysm clipping surgery with complete angiographic occlusion. Under the microscope, the balloon injected with methylene blue is visible through the arterial wall. The position and shape of the balloon can be monitored in real time without repeated angiography and fluoroscopic guidance. Two cases of intraoperative visualization balloon shift and slip into the aneurysm cavity were detected in time, and there were no cases of balloon misclipping or difficult removal. Of 17 patients, four patients (23.5%) experienced short-term complications, including pulmonary infection (11.8%), abducens nerve paralysis (5.9%), and thalamus hemorrhage (5.9%). The rate of vision recovery among patients with previous visual deficits was 70% (7 of 10 patients). The mean follow-up duration was 32.76 months. No aneurysms or neurological deficits recurred among all patients who completed the follow-up. Conclusion: Our study indicates that microsurgical clipping with the visualization balloon occlusion-assisted technique seems to be a safe and effective method for patients with large or giant paraclinoid aneurysms to reduce the surgical difficulty and simplify the operation process of microsurgical treatment alone.

Clinical Efficacy of Endoscopic Infratentorial Supracerebellar Approach for Pineal Region Tumors: A Retrospective Case-Control Study.

Tumors in the pineal region are deep, with complex surrounding anatomy, adjacent to important blood vessels and nerve structures, and surgical resection is difficult and risky. In this paper, we reviewed the literature to understand the epidemiology and clinical manifestations of pineal region tumors in the country and study the clinical indications, related problems, and successful experiences of patients with pineal region tumors treated by the transtentorial-superior approach. The clinical data of 80 patients with pineal region tumors were selected as the retrospective research objects and divided into the control group and the treatment group, with 40 cases in each group, according to the random number table method. The control group was treated using the endoscopic transtentorial approach (Poppen approach), while the treatment group was treated with the endoscopic supratentorial approach (Krause approach). The inflammatory factors, inflammatory stress response, postoperative neurological dysfunction, clinical efficacy, and poor prognosis were observed and compared between the two groups. Tumor resection and recurrence were used to compare the clinical outcomes of tumors in the pineal region. The extent of surgical resection was 100% higher in both groups, and the treatment group was comparable to the control group. The prognosis of patients after the operation was poor. Nausea and vomiting, visual disturbance, upper vision paralysis, and ataxia in the treatment group were significantly lower than those in the control group, with no statistical significance (P > 0.05). At the same time, the bone window can be reduced to reduce trauma and provide a certain reference for patients to choose a safe and complete resection method.

Combined Endovascular and Surgical Treatment for Brain Arteriovenous Malformations in Biplanar Hybrid Operating Room.

OBJECTIVE: Combined surgical and endovascular treatment for vascular disorders has become prevalent in recent years. However, reports on one-session hybrid surgery for arteriovenous malformations (AVMs) are relatively rare. The safety and efficiency of combined treatment for brain AVMs were analyzed in biplanar hybrid operating room (OR) at one stage. METHODS: We retrospectively analyzed 20 patients with AVMs undergoing combined surgical and endovascular treatment from October 2015 to June 2018. The data for resection rate, microcatheter adhesion, surgical position and postoperative outcomes were analyzed. Total resection or near-total resection was achieved in all cases. RESULTS: A total of 13 patients were under combined endovascular and surgical procedures, and 7 experienced surgery with intraoperative digital subtraction angiography. Sitting position was applied in 3 of them; 2 niduses in cerebellum, and 1 in parietal lobe. Compared with admission modified Rankin Scale (mRS) in all patients, postoperative 12-month mRS showed a significant decline. Besides, 3 patients experienced microcatheter adhesion after endovascular embolization, thereafter underwent surgical adhesion removal while nidus resection was done. CONCLUSION: Combined endovascular and surgical modality in a hybrid OR at one stage provides a safe strategy for the treatment of AVMs. The biplanar hybrid neurointerventional suite is endowed with unconstrained operating angle which enables combined endovascular and surgical treatment in sitting position. It also reduces the risk of microcatheter adhesion, which enables interventional radiologists to perform aggressively.

Endoscope-Assisted Microsurgery in Pediatric Cases With Pineal Region Tumors: A Study of 18 Cases Series.

Background: An endoscope-assisted technique was recently introduced to microsurgery (MS) and may compensate for the disadvantages of MS for deep-seated lesions. This study was performed to identify the effectiveness and safety of endoscopic-assisted microsurgery (EAM) and share our experience of EAM for pediatric cases with pineal region tumors. Method: We retrospectively analyzed the clinical data of consecutive pediatric cases with pineal region tumors treated by EAM or MS from January 2016 to June 2020. These data included the patient population, clinical manifestations, preoperative examination findings, surgical approach, pathological results, and clinical outcomes. The clinical outcomes were analyzed in the EAM group and MS group with a focus on the gross total resection (GTR) rate, postoperative hydrocephalus remission rate, and Karnofsky performance score (KPS). Studies on the surgical management of children with pineal region tumors in the last decade were reviewed. Result: Eighteen children successfully underwent tumor resection via MS (n = 8) or EAM (n = 10). The children's mean age was 11.4 ± 4.7 years, and the male to female ratio was 7:2. Seventeen patients (94.4%) complicated preoperative hydrocephalus, and 16 (88.9%) presented headache with nausea and/or vomiting. The pathological examination revealed germ cell tumors in 11 (61.1%) patients, neuroepithelial tumors in 4 (22.2%) patients, and a pineoblastoma, arachnoid cyst, and atypical teratoid rhabdoid tumor in 1 (5.6%) patient each. GTR was more commonly achieved in the EAM than MS group (80.0 vs. 50.0%, respectively), and the postoperative hydrocephalus remission rate was higher in the EAM than MS group (87.5 vs. 50.0%, respectively). At a mean follow-up time of 23.6 ± 11.5 weeks, the mean improvement of the KPS 6 months postoperatively was greater in the EAM than MS group (24.0 ± 9.7 vs. 17.5 ± 7.1 points, respectively). Conclusion: EAM combines endoscopic and microsurgical techniques and can be safely and effectively performed to achieve GTR of pineal region tumors in pediatric patients. In children with pineal region tumors who have obstructive hydrocephalus, EAM could improves hydrocephalus remission rates by checking and clearing the midbrain aqueduct under visualization.

Characteristics and operation outcomes of neuro-oncology patients after COVID-19 pandemic - A case series.

BACKGROUND: COVID-19 has been spreading worldwide at hitherto unknown speed, and the treatment of neuro-oncology patients without COVID-19 has been greatly affected. METHODS: To compare the medical records and surgical results of surgical patients before and after the pandemic. We collected a total of 80 patients form April 2020 to May 2020 after pandemic and from April 2019 to May 2019 before pandemic. The patient's demographics, past medical history, comorbidities, imaging, pathology, laboratory teat, and Karnofsky Performance Score (KPS) were analyzed. RESULTS: The most common presenting symptom was intracranial hypertension and neurological deficit. Hypertension and diabetes were the most common comorbid diseases. The pre-operation KPS were 83.21 ± 15.60, 80 ± 14.77, 78.57 ± 12.83 and 74.14 ± 12.72, respectively. The post-operation KPS were 94.64 ± 8.65, 95.45 ± 6.56, 91.43 ± 10.82 and 84.21 ± 22.55, respectively. The tumor volume was larger and the midline shift distance was greater after the pandemic than before. For pathological grade, meningiomas were mostly grade I, while gliomas were mainly grade III and IV. CONCLUSION: Although affected by the COVID-19 pandemic, patients with glioma should be operated as soon as possible to obtain better surgical results, however, for patients with meningiomas, their operation can be postponed slightly when the patients are tolerable.

Endoscopic-assisted surgery versus microsurgery for pineal region tumors: a single-center retrospective study.

Pineal region tumors are extremely deep-seated and surgically challenging. The exposure and visualization obtained by microscopic surgery are relatively limiting. The application of high-definition endoscopes has recently provided neurosurgeons with a much more magnified and clearer view of the anatomy in the pineal region. The present study was performed to compare endoscopic-assisted surgery (ES) with microsurgery (MS) for pineal region tumors. We retrospectively analyzed patients admitted to our hospital for treatment of pineal region tumors from January 2016 to June 2019. All patients consented to undergo tumor resection with ES or MS. We compared the extent of resection, postoperative rate of hydrocephalus, complications, and outcomes between the two groups to estimate the safety and efficacy of ES. In total, 41 patients with pineal region tumors were divided into 2 groups: the ES group (n = 20) and MS group (n = 21). The rate of gross total resection was significantly higher in the ES than MS group (90.0% vs. 57.1%, p = 0.04). The rate of postoperative hydrocephalus was significantly lower in the ES than MS group (11.8% vs. 52.9%, p = 0.03). No significant differences were found in complications or the Karnofsky Performance Score between the two groups. ES can be used to safely and effectively achieve complete resection of pineal region tumors. In patients with obstructive hydrocephalus, ES provides a new way to directly open the aqueduct for cerebrospinal fluid recovery following tumor resection.

Serum Lactate Dehydrogenase Level as a Prognostic Factor for COVID-19: A Retrospective Study Based on a Large Sample Size.

Background: In this study, we investigated the relationship between serum lactate dehydrogenase (LDH) level and disease progression and prognosis of patients with COVID-19. Methods: We retrospectively reviewed the information of 1,751 patients with COVID-19 from Leishenshan Hospital in Wuhan, China. Univariate and multivariate Cox regression analyses as well as Logistics regression analyses, and Kaplan-Meier curves were used to determine the association between LDH levels and the prognosis of COVID-19 patients. Results: LDH was an independent risk factor for in-hospital death no matter it was taken as classified variable and continuous variable (all P = 0.001) but not for severe or critical illness status. The Kaplan-Meier curves for LDH level showed that an elevated level of LDH was associated with in-hospital death. Conclusions: In patients with COVID-19, the increased LDH level is associated with a higher risk of negative clinical prognosis and higher mortality. This will provide a reference for clinicians and researchers to understand, diagnose, and treat patients with COVID-19. Further prospective studies with larger sample sizes are needed to verify these findings.

Combined microscope and endoscopy total resection of primary pineal malignant melanoma: case report and literature review.

BACKGROUND: Primary pineal malignant melanoma (PPMM) is a rare entity of primary central nervous system melanomas, with only 26 cases reported in the literature to date. CASE PRESENTATION: We report the case of a 65-year-old male with a PPMM who has prolonged survival of more than 104 weeks after combined microsurgical and endoscopic total resection. This is the first report: combined microscope and endoscopy total resection; PPMM in China; PPMM with total resection alone. CONCLUSION: Combined microscope and endoscopy total resection is beneficial to prolong the survival of patients. But the best approach to treatment needs verification from more clinical cases in future.

Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase.

Epidemiological studies suggest that exposure to herbicides during pregnancy might increase risk for autism spectrum disorder (ASD) in offspring. However, the precise mechanisms underlying the risk of ASD by herbicides such as glyphosate remain unclear. Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids is shown to play a key role in the development of ASD in offspring after maternal immune activation. Here, we found ASD-like behavioral abnormalities in juvenile offspring after maternal exposure to high levels of formulated glyphosate. Furthermore, we found higher levels of sEH in the prefrontal cortex (PFC), hippocampus, and striatum of juvenile offspring, and oxylipin analysis showed decreased levels of epoxy-fatty acids such as 8 (9)-EpETrE in the blood, PFC, hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure, supporting increased activity of sEH in the offspring. Moreover, we found abnormal composition of gut microbiota and short-chain fatty acids in fecal samples of juvenile offspring after maternal glyphosate exposure. Interestingly, oral administration of TPPU (an sEH inhibitor) to pregnant mothers from E5 to P21 prevented ASD-like behaviors such as social interaction deficits and increased grooming time in the juvenile offspring after maternal glyphosate exposure. These findings suggest that maternal exposure to high levels of glyphosate causes ASD-like behavioral abnormalities and abnormal composition of gut microbiota in juvenile offspring, and that increased activity of sEH might play a role in ASD-like behaviors in offspring after maternal glyphosate exposure. Therefore, sEH may represent a target for ASD in offspring after maternal stress from occupational exposure to contaminants.

Clinical Characteristics and Outcomes of 421 Patients With Coronavirus Disease 2019 Treated in a Mobile Cabin Hospital.

Background: In December 2019, a novel coronavirus-associated pneumonia, now known as coronavirus disease 2019 (COVID-19), was first detected in Wuhan, China. To prevent the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and treat patients with mild symptoms, sports stadiums and convention centers were reconstructed into mobile hospitals. Research Question: It is unknown whether a mobile cabin hospital can provide a safe treatment site for patients with mild COVID-19 symptoms. Study Design and Methods: This study retrospectively reviewed the medical records of 421 patients with COVID-19 admitted to a mobile cabin hospital in Wuhan from February 9, 2020, to March 5, 2020. Clinical data comprised patient age, sex, clinical presentation, chest imaging, nucleic acid testing, length of hospitalization, and outcomes. Results: Of the patients who were discharged from the cabin hospital, 362 (86.0%) were categorized as recovered; 14.0% developed severe symptoms and were transferred to a designated hospital. The most common presenting symptoms were fever (60.6%) and cough (52.0%); 5.2% exhibited no obvious symptoms. High fever (> 39.0°C) was more common in severe cases than in recovered cases (18.6% vs 6.6%). The distribution of lung lesions was peripheral in 85.0% of patients, multifocal in 69.4%, and bilateral in 68.2%. The most common pattern was ground-glass opacity (67.7%), followed by patchy shadowing (49.2%). The incidence of patchy shadowing was higher in patients with severe disease (66.1%) than in those who recovered (31.8%, P < .0001). The median length of hospitalization was 17 days (interquartile range, 14-19 days), and the median time taken for positive real-time reverse transcriptase polymerase chain reaction results to become negative in recovered patients was 8 days (interquartile range, 6-10 days). Interpretation: Mobile cabin hospitals provide a safe treatment site for patients with mild COVID-19 symptoms and offer an effective isolation area to prevent the spread of severe acute respiratory syndrome coronavirus 2.

CARD3 Promotes Cerebral Ischemia-Reperfusion Injury Via Activation of TAK1.

Background Although multiple signaling cascades and molecules contributing to the pathophysiological process have been studied, the treatments for stroke against present targets have not acquired significant clinical progress. Although CARD3 (caspase activation and recruitment domain 3) protein is an important factor involved in regulating immunity, inflammation, lipid metabolism, and apoptosis, its role in cerebral stroke is currently unknown. Methods and Results Using a mouse model of ischemia-reperfusion (I-R) injury based on transient blockage of the middle cerebral artery, we have found that CARD3 expression is upregulated in a time-dependent manner during I-R injury. Further animal study revealed that, relative to control mice, CARD3-knockout mice exhibited decreased inflammatory response and neuronal apoptosis, with reduced infarct volume and lower neuropathological scores. In contrast, neuron-specific CARD3-overexpressing transgenic (CARD3-TG) mice exhibited increased I-R induced injury compared with controls. Mechanistically, we also found that the activation of TAK1 (transforming growth factor-ß-activated kinase 1) was enhanced in CARD3-TG mice. Furthermore, the increased inflammation and apoptosis seen in injured CARD3-TG brains were reversed by intravenous administration of the TAK1 inhibitor 5Z-7-oxozeaenol. Conclusions These results indicate that CARD3 promotes I-R injury via activation of TAK1, which not only reveals a novel regulatory axis of I-R induced brain injury but also provides a new potential therapeutic approach for I-R injury.

Neuronal brain injury after cerebral ischemic stroke is ameliorated after subsequent administration of (R)-ketamine, but not (S)-ketamine.

Although stroke is the most common acute cerebrovascular disease, there are no currently effective therapeutic drugs for ischemic stroke. (R,S)-ketamine has been shown to protect against brain injury in rodents after middle cerebral artery occlusion (MCAO). Interestingly, we reported that (R)-ketamine has greater beneficial effects than (S)-ketamine in animal models of depression and Parkinson's disease. This study was undertaken whether two enantiomers of ketamine show neuroprotective effects in MCAO model. MCAO-induced brain injury and behavioral abnormalities in mice was attenuated by subsequent administration of (R)-ketamine (10 mg/kg, twice, 1 and 24 h after MCAO), but not (S)-ketamine (10 mg/kg, twice, 1 and 24 h after MCAO). Furthermore, the treatment with (R)-ketamine (10 mg/kg, twice, 30 min before and 24 h after MCAO) significantly protected against brain injury and behavioral abnormalities in mice after MCAO. These findings suggest that (R)-ketamine can protect against neuronal injury and behavioral abnormalities in mice after MCAO. Therefore, it is likely that (R)-ketamine could represent a therapeutic drug for ischemic stroke.

Lack of dopamine D1 receptors in the antidepressant actions of (R)-ketamine in a chronic social defeat stress model.

It is reported that dopamine D1 receptors in the medial prefrontal cortex play a role in the antidepressant actions of (R,S)-ketamine. However, its role in the antidepressant actions of (R)-ketamine, which is more potent than (S)-ketamine, is unknown. In the locomotion test, tail suspension test, forced swimming test and 1% sucrose preference test, pretreatment with dopamine D1 receptor antagonist SCH-23390 did not block the antidepressant effects of (R)-ketamine in the susceptible mice after chronic social defeat stress. These findings suggest that dopamine D1 receptors may not play a major role in the antidepressant actions of (R)-ketamine.

Comparison of antidepressant and side effects in mice after intranasal administration of (R,S)-ketamine, (R)-ketamine, and (S)-ketamine.

The N-methyl-d-aspartate receptor (NMDAR) antagonist (R,S)-ketamine produces rapid and sustained antidepressant effects in treatment-resistant patients with depression although intranasal use of (R,S)-ketamine in ketamine abusers is popular. In March 5, 2019, nasal spray of (S)-ketamine for treatment-resistant depression was approved as a new antidepressant by the US Food Drug Administration. Clinical study of (R)-ketamine is underway. In a chronic social defeat stress (CSDS) model, we compared the antidepressant effects of (R,S)-ketamine, (R)-ketamine, and (S)-ketamine after a single intranasal administration. Furthermore, we also compared the side effects (i.e., locomotion, prepulse inhibition (PPI), abuse liability) of these three compounds in mice. The order of potency of antidepressant effects after a single intranasal administration was (R)-ketamine > (R,S)-ketamine > (S)-ketamine. In contrast, the order of locomotor activity and prepulse inhibition (PPI) deficits after a single intranasal administration was (S)-ketamine > (R,S)-ketamine > (R)-ketamine. In the conditioned place preference (CPP) test, both (S)-ketamine and (R,S)-ketamine increased CPP scores in mice after repeated intranasal administration, in a dose dependent manner. In contrast, (R)-ketamine did not increase CPP scores in mice. These findings suggest that intranasal administration of (R)-ketamine would be a safer antidepressant than (R,S)-ketamine and (S)-ketamine.

Beneficial effects of (R)-ketamine, but not its metabolite (2R,6R)-hydroxynorketamine, in the depression-like phenotype, inflammatory bone markers, and bone mineral density in a chronic social defeat stress model.

Inflammatory bone markers may play a role in the antidepressant actions of (R)-ketamine in susceptible mice after chronic social defeat stress (CSDS). In this study, we compared the effects of (R)-ketamine and its final metabolite (2R,6R)-hydroxynorketamine (HNK) in depression-like phenotypes, inflammatory bone markers and bone mineral density (BMD) in CSDS susceptible mice. We measured plasma levels of inflammatory bone markers, which included osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL), and osteopontin after behavioral tests. (R)-ketamine, but not (2R,6R)-HNK, elicited rapid and sustained antidepressant effects in CSDS susceptible mice. Furthermore, (R)-ketamine, but not (2R,6R)-HNK, significantly improved the increased plasma levels of RANKL and decreased OPG/RANKL ratio in CSDS susceptible mice. Moreover, (R)-ketamine, but not (2R,6R)-HNK, significantly attenuated the decreased BMD in CSDS susceptible mice. These findings demonstrate that (R)-ketamine may have beneficial effects in depression-like phenotype and abnormalities in bone functions of CSDS susceptible mice. It is, therefore, likely that (R)-ketamine would be a potential therapeutic drug for abnormalities in bone metabolism in depressed patients.

Intracerebral hemorrhage cadaver model for training in hematoma evacuation under endoscopy.

Neuroendoscopic surgery has been performed as an effective method for intracerebral hemorrhage (ICH). This study describes the know-how of constructing the ICH cadaver model and the training on the main neuroendoscopic procedures for ICH. During the training, operation time of twenty trainees in main stages of craniotomy and corticotomy (stage 2), and hematoma evacuation under endoscopy (stage 3) was recorded. To distinguish factors influencing trainees' surgical proficiency, operation time was calculated according to seniority, experience in neuroendoscopic surgery and training sequence. Questionnaire about validity of model was conducted eventually. Ten ICH cadaver models with bilateral hematoma were constructed. Seven trainees worked with seniority >5 years and eleven had experience in neuroendoscopic surgery. Operation time ranged from 20.6 to 33.4 min in stage 2 and 18.5 to 24.9 min in stage 3. In stage 2, less operation time was needed for trainees with seniority >5 years comparing to trainees with seniority ≦5 years (22.56 ±â€¯1.29 vs 29.25 ±â€¯3.02 min, p < 0.01). In stage 3, significant difference of operation time was found between trainees with experience in neuroendoscopic surgery and trainees without the experience (20.08 ±â€¯1.22 vs 22.02 ±â€¯1.82 min, p = 0.014), and the same between trainees in latter group and in former group (19.75 ±â€¯0.80 vs 22.54 ±â€¯1.45 min, p < 0.01). Questionnaire feedback proved high degree of satisfaction about the training model. Therefore, the ICH cadaver model can assist neurosurgeons with neuroendoscopic treatment learning sessions. Simulation and improvement in neuroendoscopic surgical techniques for ICH treatment were possible with the help of ICH cadaver model.

Key role of soluble epoxide hydrolase in the neurodevelopmental disorders of offspring after maternal immune activation.

Maternal infection during pregnancy increases risk of neurodevelopmental disorders such as schizophrenia and autism spectrum disorder (ASD) in offspring. In rodents, maternal immune activation (MIA) yields offspring with schizophrenia- and ASD-like behavioral abnormalities. Soluble epoxide hydrolase (sEH) plays a key role in inflammation associated with neurodevelopmental disorders. Here we found higher levels of sEH in the prefrontal cortex (PFC) of juvenile offspring after MIA. Oxylipin analysis showed decreased levels of epoxy fatty acids in the PFC of juvenile offspring after MIA, supporting increased activity of sEH in the PFC of juvenile offspring. Furthermore, expression of sEH (or EPHX2) mRNA in induced pluripotent stem cell-derived neurospheres from schizophrenia patients with the 22q11.2 deletion was higher than that of healthy controls. Moreover, the expression of EPHX2 mRNA in postmortem brain samples (Brodmann area 9 and 40) from ASD patients was higher than that of controls. Treatment with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent sEH inhibitor, in juvenile offspring from prenatal day (P) 28 to P56 could prevent cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial PFC of adult offspring after MIA. In addition, dosing of TPPU to pregnant mothers from E5 to P21 could prevent cognitive deficits, and social interaction deficits and PV immunoreactivity in the medial prefrontal cortex of juvenile offspring after MIA. These findings suggest that increased activity of sEH in the PFC plays a key role in the etiology of neurodevelopmental disorders in offspring after MIA. Therefore, sEH represents a promising prophylactic or therapeutic target for neurodevelopmental disorders in offspring after MIA.

Increased expression of inwardly rectifying Kir4.1 channel in the parietal cortex from patients with major depressive disorder.

BACKGROUND: The inwardly rectifying K+ channel subtype Kir4.1 has been well studied in the astrocyte within brain; however, the precise role of this protein in psychiatric disorders is unknown. Kir4.1 is also known to interact with GABAB receptors which may be implicated in psychiatric disorders. Here we studied whether expression of Kir4.1 and GABAB receptors was altered in the postmortem brain samples (parietal cortex and cerebellum) from patients with major psychiatric disorders. METHODS: Protein expression of Kir4.1 and GABAB receptors in the parietal cortex and cerebellum from control, major depressive disorder (MDD), schizophrenia (SZ), and bipolar disorder (BD) groups was measured. RESULTS: Levels of Kir4.1 in the parietal cortex from MDD group, but not SZ and BD groups, were significantly higher than the control group. Furthermore, levels of GABAB receptor subunit 1 in the parietal cortex from MDD group and SZ group, but not BD group, were also significantly higher than the control group. Interestingly, there was a positive correlation between Kir4.1 protein and GABAB receptor subunit 1 in the parietal cortex from control group, but not MDD group. LIMITATIONS: The small number in each group may limit our interpretation. Only two brain regions were analyzed. CONCLUSIONS: Abnormalities in the interaction of Kir4.1 and GABAB receptor in the parietal cortex might play a role in the pathophysiology of MDD.