Exposure to Polystyrene Microplastics Promotes the Progression of Cognitive Impairment in Alzheimer's Disease: Association with Induction of Microglial Pyroptosis.

We focused on investigating the effects and mechanisms of polystyrene (PS) microplastics in Alzheimer's disease (AD). PS could promote the cognitive impairment in mice and antagonize the action of PS. Meanwhile, it could promote microglial pyroptosis and aggravate neuroinflammation. In vitro results also showed that PS induced pyroptosis of BV2 and RAW264.7, after GSDMD silencing, such pyroptosis was inhibited. Our study found that PS aggravated neuroinflammation by inducing microglial pyroptosis, thereby promoting the progression of cognitive impairment in AD. This finding offers new support and reference for the induction of AD progression by environmental factors.

LncRNA-AC020978 Promotes Metabolic Reprogramming in M1 Microglial Cells in Postoperative Cognitive Disorder via PKM2.

The present work aimed to explore the role of long non-coding RNA (lncRNA)-AC020978 in postoperative cognitive disorder (POCD) and the underlying mechanism. The POCD mouse model was constructed through isoflurane anesthesia + abbreviated laparotomy. The AC020978 expression in brain tissue was silenced after lentivirus injection, then Morris water maze test was conducted to detect the cognitive disorder level, flow cytometry was performed to analyze M1 macrophage level, ELISA was carried out to measure inflammatory factor levels, H&E, Nissl and immunohistochemical staining was performed to detect the pathological changes in brain tissue, and Western blotting assay was adopted to detect protein expression. In addition, microglial cells were cultured in vitro, after lentivirus infection, the effect of AC020978 on the M1 polarization of microglial cells and glycolysis was observed. AC020978 overexpression promoted POCD progression and aggravated cognitive disorder in mice; in addition, the proportion of peripheral and central M1 cells increased, the inflammatory factor levels were upregulated, and microglial cells were activated. By contrast, AC020978 silencing led to cognitive disorder in mice and suppressed microglial cell activation and M1 polarization. In vitro experimental results indicated that AC020978 promoted the expression and phosphorylation of PKM2, which promoted inflammatory response through enhancing microglial cell glycolysis and M1 polarization. AC020978 interacts with PKM2 to promote the glycolysis and M1 polarization of microglial cells, thus regulating cognitive disorder and central inflammation in POCD.

Usability of serum inter-α-trypsin inhibitor heavy chain 4 as a biomarker for assessing severity and predicting functional outcome after human aneurysmal subarachnoid hemorrhage: A prospective observational cohort study at a single institution.

BACKGROUND: Inter-α-trypsin inhibitor heavy chain 4 (ITIH4) may harbor anti-inflammatory activities. We sought to discern the predictive significance of serum ITIH4 for delayed cerebral ischemia (DCI) and clinical outcomes of human aneurysmal subarachnoid hemorrhage (aSAH). METHODS: At a single institution, we performed a prospective and observational cohort study of 148 patients with aSAH and 52 healthy controls. Poststroke six-month extended Glasgow Outcome Scale (GOSE) score of 1-4 was designated as a poor prognosis. Prognosis associations were verified using multivariate analysis. RESULTS: As compared to controls, patients had significantly declined serum ITIH4 concentrations from admission until day 10, with the lowest concentrations at days 1-3 after stroke. Serum ITIH4 concentrations, which were substantially decreased with the increasing Hunt-Hess scores or modified Fisher scores, were independently correlated with the two scores. Moreover, serum ITIH4 concentrations, which were markedly elevated in the order of GOSE scores from 1 to 8, together with Hunt-Hess scores and modified Fisher scores were independently related to GOSE scores and poor prognosis. However, serum ITIH4 concentrations were not independently predictive of DCI. Prediction model of poor prognosis integrating the preceding three variables were delineated using the nomogram, were verified under the calibration curve, and displayed high discriminatory efficiencies under the receiver operating characteristic curve. CONCLUSIONS: A significant decline of serum ITIH4 concentrations during the early phase after aSAH was closely related to severity and poor prognosis, assuming that serum ITIH4 may represent a promising prognostic biomarker of aSAH.

Intracranial Rosai­Dorfman disease complicated by mucosa­associated lymphoid tissue: A case report.

Intracranial Rosai-Dorfman disease (RDD) is a rare, self-limiting histiocytic disease of unknown etiology. Extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is also rare and intracranial RDD complicated by MALT lymphoma is even rarer. The present study reports a case of a 55-year-old female who was admitted to The Second Affiliated Hospital of Jiaxing University (Jiaxing, China) with headache for half a month and ptosis of the right eyelid for 4 days. Computerised tomography and magnetic resonance imaging revealed a right parasellar tumor and, subsequently, subtotal resection of the tumor was performed. Postoperative pathology revealed intracranial RDD complicated by MALT lymphoma. The patient received chemotherapy after surgery and achieved good therapeutic effects. After 12 months of follow-up, the residual tumor disappeared and the ptosis prominently improved. To the to the best of the authors' knowledge, the present case is the first reported case of an adult intracranial RDD complicated by MALT lymphoma.

Case report: Diagnosis and treatment of delayed epidural pyogenic abscess after brain tumor operation: a report of 5 cases and review of the literature.

Objective: To explore the clinical manifestations and treatment of delayed epidural pyogenic abscess after brain tumor surgery. Method: To retrospectively analyze the medical records of 5 patients with delayed epidural pyogenic abscess after brain tumor surgery in our hospital from January 2010 to December 2020, including clinical manifestations, laboratory results, imaging findings, treatment measures, prognosis, etc. The causes of epidural abscesses were analyzed, and the treatment methods and prognosis were evaluated. Result: Among the 5 cases, there were 4 male and 1 female patient, aged 52-75 years. Three cases were gliomas and 2 cases were meningiomas. Four cases received postoperative radiotherapy, and 1 case had open frontal sinus during operation. None of the surgical incisions were infected. The time between the tumor surgery and the discovery of an epidural abscess was 1.5 to 24 months. All 5 patients had headaches, 1 case had a fever, and 2 cases had limb dysfunction. Three cases had elevated blood inflammatory markers. MRI- DWI showed restricted diffusion. All 5 patients underwent surgery, 4 patients had bone flap removed, and 1 patient had bone flap retained. Bacterial culture was positive in 3 cases and negative in 2 cases. All 5 cases were cured, followed up for 1.5-9 years, and no epidural abscess recurred. Conclusion: The clinical manifestations and laboratory results of delayed epidural pyogenic abscess after brain tumor surgery are not specific, but MRI-DWI has specificity. Postoperative radiotherapy for brain tumors and intraoperative opening of the frontal sinus may be associated with delayed epidural pyogenic abscess. For patients with normal skin flap and no serious inflammation of the bone flap, clinicians can attempt to preserve the bone flap.

TL1A promotes the postoperative cognitive dysfunction in mice through NLRP3-mediated A1 differentiation of astrocytes.

AIM: We investigated the mechanism, whereby tumor necrosis factor-like ligand 1A (TL1A) mediates the A1 differentiation of astrocytes in postoperative cognitive dysfunction (POCD). METHODS: The cognitive and behavioral abilities of mice were assessed by Morris water maze and open field tests, while the levels of key A1 and A2 astrocyte factors were detected by RT-qPCR. Immunohistochemical (IHC) staining was used to examine the expression of GFAP, western blot was used to assay the levels of related proteins, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines. RESULTS: The results showed that TL1A could promote the progression of cognitive dysfunction in mice. Astrocytes differentiated into A1 phenotype, while unobvious changes were noted in astrocyte A2 biomarkers. Knockout of NLRP3 or intervention with NLRP3 inhibitor could inhibit the effect of TL1A, improving the cognitive dysfunction and suppressing the A1 differentiation. CONCLUSION: Our results demonstrate that TL1A plays an important role in POCD in mice, which promotes the A1 differentiation of astrocytes through NLRP3, thereby exacerbating the progression of cognitive dysfunction.

Aurantiamide suppresses the activation of NLRP3 inflammasome to improve the cognitive function and central inflammation in mice with Alzheimer's disease.

AIM: This study was aimed at exploring the mechanism by which aurantiamide (Aur) targeted NLRP3 to suppress microglial cell polarization. METHODS: The 7-month-old APP/PS1 mice and C57BL/6 mice were applied to be the study objects, and Aur was administered intragastrically to APP/PS1 mice at 10 mg/kg and 20 mg/kg. The changes in the neurocognitive function of mice were measured by Morris Water Maze (MWM) test. In the in vitro experiments, the mouse BV2 cells were employed as the study objects, which were subject to treatment with 10 µM and 20 µM Aur and induced with LPS and IFN-γ in order to activate BV2 cells and induce their M1 polarization. RESULTS: Aur was found to suppress the M1 polarization of mouse microglia, reduce central neuroinflammation, and improve the cognitive function in mice. Meanwhile, Aur suppressed the activation and the expression of NLRP3 inflammasome. The results of experiments in vitro demonstrated that Aur inhibited the activation and M1 polarization of BV2 cells. CONCLUSION: Aur targets NLRP3 and suppresses the activation of NLRP3 inflammasome.

Benign cervical intramedullary cyst without an epithelial lining：a case report.

This paper presents a female, benign intramedullary cyst case aged 66-year-old. During the operation, it was found that the cystic wall was very thin, and the cystic fluid was colorless and transparent. The lesion with the capsule was removed partially. Surprisingly, there was no epithelial lining on the capsule wall. It is very rare and different from the benign intramedullary cysts reported in the literature.

Cryptococcal granuloma of the the basal ganglia with fatal haemorrhage after stereotactic biopsy: case report.

This paper presents a male, immunocompetent case aged 62-year-old with cryptococcal granuloma in the basal ganglia. No cryptococcal infection occurred in other areas. The diagnosis was made by biopsy. Cryptococcal granuloma was tough and unsuitable for sterotactic biopsy. The patient died of postoperative bleeding and we suggest avoiding stereotactic biopsy of lesions suspected of being cryptococcal granulomas.

Intracranial inflammatory myofibroblastic tumor: a report of two cases.

We report two cases of Intracranial inflammatory myofibroblastic tumor (IMT) with recurrent, cystic, and venous sinus occlusion. The cases show imaging progression from a small lesion (case 1) or absence of lesions (case 2). One of cases recurred 2 years after surgery and was treated with corticosteroids but the tumor was still growing and was resected again. We think the best treatment for IMT is surgical resection.

Aurantiamide promotes M2 polarization of microglial cells to improve the cognitive ability of mice with Alzheimer's disease.

This work aimed to investigate the effect of aurantiamide (Aur) in promoting the M2 polarization of microglial cells to improve the cognitive ability of mice with Alzheimer's disease (AD). The M2 polarization of BV2 cells was induced by interleukin-4 (IL-4) treatment.Aur promoted the M2 polarization of BV2 cells, and up-regulated the expression of CD206 and SOCS3. In the meantime, it increased TGF-ß1, Arg-1 and IL-10 levels, and promoted the polarization of JAK1-STAT6. Treatment with STAT6 inhibitor antagonized the effect of Aur. Besides, the cognitive ability of AD mice was improved after Aur treatment, meanwhile, the expression of CD206 was up-regulated, while that of IBA-1 was down-regulated. Aur promotes the M2 polarization of microglial cells to improve the cognitive ability of AD mice, and such effect is related to the STAT6 signal.

Hepcidin regulates neuronal ferroptosis: A mechanism for postoperative cognitive dysfunction.

Toll-like receptor 4 (TLR4) is a signaling molecule responsible for the expression of hepcidin (Hepc), while myeloid differentiation protein 2 (MD2) is one major accessory protein of TLR4. This study focuses on exploring the neurocyte ferroptosis mediated through the regulation of Hepc expression by MD2, which is also one of the mechanisms for postoperative cognitive dysfunction (POCD). An experimental study was carried out using aged wild-type (Wt) and MD2 transgenic (Tg) mice. The neurocyte ferroptosis and POCD in the mice were assessed following splenectomy. Morris water maze was utilized to assess the neurocognitive abilities, hematoxylin and eosin (H&E) assay was performed to examine histopathology, and Nissl staining was used to evaluate the neurocyte damage. The Fe2+ , superoxide dismutase(SOD), malondialdehyde (MDA), glutathione(GSH), and glutathione peroxidase 4 (GPX4) levels were determined with kits. The expressions of transferrin receptor (TFR), Hepc, and MD2 were measured by Western blotting, while the expressions of TFR and GPX4 were measured by immunohistochemical staining. In Tg mice, we observed neurocyte ferroptosis and POCD following treatment with an MD2 inhibitor. PC12 cells were used as a neurocyte model. Ferroptosis was induced after treatment with an MD2 inhibitor, and the cell viability was assayed by Cell Counting Kit-8. Immunofluorescent staining was used to measure the TFR and GPX4 expressions. Meanwhile, the intracellular levels of Fe2+ , SOD, MDA, GSH, GPX4, and Hepc were also measured. POCD occurred among aged Wt and Tg mice. The Tg-POCD mice had more apparent POCD than the Wt-POCD mice. Nissl and H&E staining revealed neurocyte damage in brain tissues. Besides this, the Fe2+ and MDA expressions were upregulated, while the SOD, GSH, and GPX4 expressions were downregulated. Elevations in tissue levels of TFR, Hepc, and MD2 were observed, which were higher than those of Wt-POCD mice. After treatment with an MD2 inhibitor, the POCD could be prominently ameliorated in Tg-POCD mice, the Fe2+ and MDA levels could be reduced, while the SOD, GSH, and GPX4 levels could be elevated. In the PC12 model, ferroptosis could be suppressed by inhibiting the expression of MD2. MD2 is capable of regulating neurocyte ferroptosis by promoting Hepc expression, which has great potential as a novel target for POCD therapy.

Salvianolic acid C improves cerebral ischemia reperfusion injury through suppressing microglial cell M1 polarization and promoting cerebral angiogenesis.

This study aimed to investigate the mechanism of salvianolic acid C (SAC), the active ingredient in Salvia miltiorrhiza, in improving cerebral ischemia injury. The mouse microglial cells BV2 and mouse endothelial cells bEnd.3 were used as the objects of study. LPS/IFN-γ was applied to simulate the BV2 polarization, and bEnd.3 cells were treated under hypoxic condition. The BV2 cell polarization level was measured through flow cytometry (FCM), the TLR4 and MyD88 expression levels were detected by fluorescence staining, whereas the expression of inflammatory factors TNF-α, IL-6 and IL-1ß was analyzed through ELISA. Tubule formation assay was also conducted to observe the tubule formation ability of bEnd.3 cells in vitro, and the level of VEGFR2 was detected by fluorescence staining. Cells were treated with the PKM2 inhibitor IN3, aiming to observe the influence of SAC on glycolysis of BV2 cells. In addition, the mouse model of cerebral ischemia was constructed through the middle cerebral artery occlusion (MCAO) method, and the pathological changes in brain tissues were detected after SAC intervention. Meanwhile, the levels of IBA-1, CD31 and ZO-1 were determined through histochemical staining. Nissl staining to detect nerve cell damage. In BV2 cell experiment, SAC suppressed the M1 polarization of BV2 cells, reduced the inflammatory factor levels, and inhibited the activation of TLR4 signal through suppressing glycolysis. When PKM2 was suppressed, the effects of SAC were antagonized. In the bEnd.3 model, SAC promoted tubule formation in bEnd.3 cells under hypoxic condition, and increased the expression of VEGFR2 and Notch1. In the mouse model, SAC improved the neurological function in MCAO mice, and inhibited the activation of microglial cells and the expression of inflammatory factors. At the same time, SAC up-regulated the expression of ZO-1 and CD31, and maintained the blood-brain barrier (BBB) function. As a major component of Salvia miltiorrhiza, SAC can suppress microglial cell polarization and promote tubule formation in endothelial cells to exert the neurological repair function in cerebral ischemia. SAC is a multi-functional neuroprotective small molecule.

A simple and successful treatment for rupture and defect of the posterior third superior sagittal sinus caused by open depressed skull fracture: A case report.

It is extremely dangerous to treat the posterior third of the superior sagittal sinus (PTSSS) surgically, since it is usually not completely ligated. In this report, the authors described the case of a 27-year-old man with a ruptured and defective PTSSS caused by an open depressed skull fracture, which was treated by ligation of the PTSSS and the patient achieved a positive recovery. The patient's occiput was hit by a height-limiting rod and was in a mild coma. A CT scan showed an open depressed skull fracture overlying the PTSSS and a diffuse brain swelling. He underwent emergency surgery. When the skull fragments were removed, a 4 cm segment of the superior sagittal sinus (SSS) and the adjacent dura mater were removed together with bone fragments. Haemorrhage occurred and blood pressure dropped. We completed the operation by ligating the severed ends of the fractured sagittal sinus. One month after the operation, apart from visual field defects, he recovered well. In our opinion, in primary hospitals, when patients with severely injured PTSSS cannot sustain a long-time and complicated operation, e.g., the bypass using venous graft, and face life-threatening conditions, ligation of the PTSSS is another option, which may unexpectedly achieve good results.

Adult rhabdomyosarcoma originating in the temporal muscle, invading the skull and meninges: A case report.

BACKGROUND: Rhabdomyosarcoma (RMS) is a rare malignant tumor of mesenchymal origin that mainly affects children. Spindle cell/sclerosing RMS (SSRMS) is even rarer. It is a new subtype that was added to the World Health Organization disease classification in 2013. To the best of our knowledge, this is the first reported case of adult SSRMS disease classification originating in the temporal muscle. CASE SUMMARY: SSRMS originating in the temporal muscle of a male adult enlarged rapidly, destroyed the skull, and invaded the meninges. The tumor was completely removed, and the postoperative pathological diagnosis was SSRMS. Postoperative recovery was good and chemotherapy and radiotherapy were given after the operation. Followed up for 3 mo, no tumor recurred. CONCLUSION: RMS is one of the differential diagnoses for head soft tissue tumors with short-term enlargement and skull infiltration. Preoperative computed tomography or magnetic resonance imaging is necessary for early detection of tumor invasion of the skull and brain tissue.

Traumatic pseudoaneurysms of external carotid artery branch: Case series and treatment considerations.

PURPOSE: To explore the diagnosis and treatment of traumatic external carotid branch pseudoaneurysms. METHODS: Eleven cases of traumatic external carotid artery branch pseudoaneurysms were admitted in our hospital. Digital subtraction angiography was performed in all patients. It revealed that the pseudoaneurysms originated from the internal maxillary artery in 5 cases, superficial temporal artery in 5 cases and occipital artery in 1 case. Five cases of internal maxillary artery pseudoaneurysms and 2 cases of superficial temporal artery pseudoaneurysms were treated by embolization; the other 3 cases were surgically resected. RESULTS: Complete cessation of nasal bleeding was achieved in all the 5 pseudoaneurysms of internal maxillary artery after the endovascular therapies. Scalp bleeding stopped and scalp defect healed up in 2 patients with superficial temporal artery pseudoaneurysms treated by interventional therapy. All patients were followed up for 0.5-2.0 years without recurrence of nosebleed and scalp lump. CONCLUSION: For patients with repeated severe epistaxis after craniocerebral injury, digital subtraction angiography should be performed as soon as possible to confirm traumatic pseudoaneurysm. Endovascular therapy is an effective method for traumatic internal maxillary artery pseudoaneurysms. For patients with scalp injuries and pulsatile lumps, further examinations including digital subtraction angiography should be performed to confirm the diagnosis. Surgical treatment or endovascular therapy for scalp traumatic pseudoaneurysm is effective.

Pyroptosis executive protein GSDMD as a biomarker for diagnosis and identification of Alzheimer's disease.

OBJECTIVE: This study was mainly conducted to explore the expression changes of GSDMD and conventional markers (including T-Tau, Tau181p, and Aß1-42 ) in the cerebrospinal fluid among patients with Alzheimer's disease (AD) and vascular dementia (VD), followed by determination of role of GSDMD in diagnosing and identifying AD and VD. METHODS: In this study, 60 patients with VD, 60 patients with AD, and 50 healthy controls were enrolled. Lumbar puncture was performed to collect cerebrospinal fluid samples. Patients with VD and patients with AD were evaluated using the Mini-Mental State Examination (MMSE) scale, Montreal Cognitive Assessment (MoCA) scale, Clinical Dementia Rating (CDR) scale, Activity of Daily Living (ADL) scale, and Neuropsychiatric Inventory (NPI) questionnaire, aiming to determine the behavioral ability of patients. ELISA kit was purchased to determine the levels of GSDMD, T-Tau, Tau181p, and Aß1-42 in cerebrospinal fluid, and the expression of inflammatory factors, IL-1ß and IL-6, was also detected. RESULTS: (1) The levels of GSDMD, T-Tau, and Tau181p in the cerebrospinal fluid were higher in patients with AD than those of patients with VD and healthy controls, while the levels of Aß1-42 in the cerebrospinal fluid were lower in patients with AD than that in healthy controls and patients with VD. (2) GSDMD had good diagnostic accuracy in AD. Additionally, GSDMD, T-Tau, Tau181p, and Aß1-42 had good discrimination accuracy in distinguishing AD and VD. (3) The expression levels of inflammatory factors (IL-1ß and IL-6) in cerebrospinal fluid were higher in patients with AD than those of healthy controls and patients with VD, which were positively correlated with GSDMD expression. CONCLUSION: The expression of GSDMD was increased in patients with AD, which could be used as a biomarker for AD diagnosis and identification from VD.

Endoscopic transsphenoidal approach to a sphenoid sinus inverted papilloma combined with pituitary adenoma: a case report.

Sphenoid sinus inverted papilloma (IP) is a very infrequent tumor, and the combination of sphenoidal IP with pituitary tumor is extremely rare. In this report, the authors describe the case of a 63-year-old male with oculomotor nerve palsy in the left eye due to sellar region tumor. After endoscopic transsphenoidal surgery, the postoperative pathological examination confirmed the co-occurrence of an sphenoidal IP and pituitary adenoma. To our knowledge, the present case is the second reported case of an IP with a pituitary adenoma.