SDF-1/CXCR4 axis participants in the pathophysiology of adult patients with moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) is characterized by an abundance of moyamoya vessels; however, the precise mechanism driving the spontaneous angiogenesis of these compensatory vessels remains unclear. Previous research has established a link between the stromal cell-derived factor-1 (SDF-1)/ CXC receptor 4 (CXCR4) axis and angiogenesis under hypoxic conditions. Nevertheless, the alterations in this axis within the cerebrospinal fluid, arachnoid membranes and vascular tissue of MMD patients have not been fully investigated. METHODS: Our study enrolled 66 adult MMD patients and 61 patients with atherosclerotic vascular disease (ACVD). We investigated the SDF-1 concentration in cerebrospinal fluid (CSF) and CXCR4 expression level on the arachnoid membranes and vascular tissue. We utilized enzyme-linked immunosorbent assay and immunohistochemistr. Additionally, we cultured and stimulated human brain microvascular endothelial cells (HBMECs) and smooth muscle cells (SMCs) under oxygen and glucose deprivation (OGD) conditions followed by reoxygenation, to examine any changes in the SDF-1/CXCR4 axis. RESULTS: The results demonstrated an elevation in the level of SDF-1 in CSF among MMD patients compared to those with ACVD. Moreover, the expression of CXCR4 in arachnoid membranes and vascular tissue showed a similar trend. Furthermore, the content of CXCR4 in HBMECs and SMCs increased with the duration of ischemia and hypoxia. However, it was observed that the expression of CXCR4 decreased at OGD/R 24h compared to OGD 24h. The temporal pattern of SDF-1 expression in HBMECs and SMCs mirrored that of CXCR4 expression. CONCLUSION: These findings indicate a critical role for the SDF-1/CXCR4 axis in the angiogenesis of moyamoya disease.

Comparison of IMD and ICG videoangiography in combined bypass surgery: a single-center study.

BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) bypass combined with an encephaloduromyosynangiosis (EDMS) had gained significant role in treating chronic cerebral ischemia. Invasiveness and costs of intraoperative digital subtraction angiography (DSA) limited its application in operations. OBJECTIVE: To find the reliable parameters for determining bypass patency with intraoperative micro-Doppler (IMD) sonography and compare the diagnostic accuracy of indocyanine green (ICG) videoangiography with IMD in combined bypass. METHOD: One hundred fifty bypass procedures were included and divided into patent and non-patent groups according to postoperative computed tomography angiography (CTA) within 72 h. The surgical process was divided into four phases in the following order: preparation phase (phase 1), anastomosis phase (phase 2), the temporalis muscle closure phase (phase 3), and the bone flap closure phase (phase 4). The IMD parameters were compared between patent and non-patent groups, and then compared with the patency on CTA by statistical analyses. IMD with CTA, ICG videoangiography with CTA, IMD with ICG videoangiography were performed to assess bypass patency. The agreement between methods was evaluated using kappa statistics. RESULTS: No significant differences of baseline characteristics were found between patent and non-patent group. Parameters in the STA were different between patent and non-patent groups in phases 2, 3, and 4. In patent group, Vm was apparently higher and PI was lower in phases 2, 3, and 4 compared with phase 1 (P < .001). In non-patent group, no differences of Vm and PI were found within inter-group. The best cutoff value of IMD in the STA to distinguish patent from non-patent bypasses was Vm in phase 4 > 17.5 cm/s (sensitivity 94.2%, specificity 100%). In addition, the agreement for accessing bypass patency was moderate between ICG videoangiography and CTA (kappa = 0.67), IMD and ICG videoangiography (kappa = 0.73), and good between IMD and CTA (kappa = 0.86). CONCLUSION: ICG videoangiography could directly display morphology changes of bypass. IMD could be used for providing half-quantitative parameters to assess bypass patency. Vm in phase 4 > 17.5 cm/s suggesting the patency of bypass on CTA would be good. Also, compared with ICG videoangiography, IMD had more accuracy.

Resection of ruptured aneurysm associated with bilateral anomalous posterior inferior cerebellar anastomotic arteries: case report and review of literature.

Introduction: Aneurysms on the posterior inferior cerebellar artery (PICA) may not be the major part of intracranial aneurysm. Especially, an aneurysm located on the bilateral posterior inferior cerebellar anastomotic artery has abnormal anatomical characteristics in the vessel wall and then causes stroke including subarachnoid hemorrhage. This case report explores the direct resection of a ruptured aneurysm associated with the bilateral anomalous anastomotic artery of PICA. Methods: The case report discusses a 53-year-old woman who suffered from sudden severe headache and vomiting for more than 3 h admitted to our hospital. Emergency computed tomography (CT) revealed subarachnoid hemorrhage (SAH) in the third and fourth ventricles. Preoperative 3 Dimensions-digital subtraction angiography (3-D DSA) indicated a ruptured aneurysm located on the bilateral posterior inferior cerebellar anastomotic artery. Postoperative pathological findings indicated the characteristics of parent artery PICA and control aneurysm. The authors performed an overview of PICA aneurysms with anomalous variation in the Pubmed, Web of Science, and Medline databases. The search was until 1 August 2023. Related terms "posterior inferior cerebellar artery" And "aneurysm" AND "anatomical variants" were used to search the review. The reasons for anomalous variation anastomosis between bilateral PICAs were analyzed. Results: The aneurysm was resected successfully. Post-operative 3-D DSA revealed the disappearance of the aneurysm. The vessel wall of anastomotic PICA showed neovascularized hyperplasia, abnormal arrangement of smooth muscle, CD31+ endothelial cells, and SMA+ smooth muscle cells. In contrast, when it came to aneurysm, the wall at the location of the fracture thinned, which could be used to explain that the local nodular protrusion was formed and CD31+ endothelial cells existed. No neurological deficits were found at her 1-year follow-up visit (mRS score of 0). Conclusion: Direct resection of ruptured aneurysm associated with bilateral anomalous posterior inferior cerebellar anastomotic arteries was an effective treatment and careful consideration of the anatomical characteristics concerning the interesting aneurysm and the variant PICA was critical for sate treatment. Also, the literature on the lesion was reviewed.

LSM2 is associated with a poor prognosis and promotes cell proliferation, migration, and invasion in skin cutaneous melanoma.

BACKGROUND: Skin cutaneous melanoma (SKCM) is an extremely malignant tumor that is associated with a poor prognosis. LSM2 has been found to be related to different types of tumors; however, its role in SKCM is poorly defined. We aimed to determine the value of LSM2 as a prognostic biomarker for SKCM. METHODS: The expression profile of LSM2 mRNA was compared between tumor and normal tissues in public databases, such as TCGA, GEO, and BioGPS. LSM2 protein expression was explored using immunohistochemistry (IHC) on a tissue microarray containing 44 SKCM tissues and 8 normal samples collected at our center. Kaplan-Meier analysis was performed to assess the prognostic value of LSM2 expression in patients with SKCM. SKCM cell lines with LSM2 knockdown were used to determine the effects of LSM2. Cell counting kit-8 (CCK8) and colony formation assays were conducted to assess cell proliferation, whereas wound healing and transwell assays were carried out to assess the migration and invasion abilities of SKCM cells. RESULTS: LSM2 was more highly expressed at the mRNA and protein levels in SKCM than that in normal skin. Moreover, elevated expression of LSM2 was associated with shorter survival time and early recurrence in patients with SKCM. The in vitro results revealed that the silencing of LSM2 in SKCM cells significantly inhibited cell proliferation, migration, and invasion. CONCLUSION: Overall, LSM2 contributes to malignant status and poor prognosis in patients with SKCM and may be identified as a novel prognostic biomarker and therapeutic target.

Data-Independent Acquisition-Based Serum Proteomic Profiling of Adult Moyamoya Disease Patients Reveals the Potential Pathogenesis of Vascular Changes.

Moyamoya disease (MMD) is a chronic cerebrovascular disease with unknown etiology. The pathogenesis of vascular changes remains unclear. Ischemic and hemorrhagic adult MMD patients and healthy volunteers were enrolled to collect serum for data-independent acquisition (DIA)-based proteomic analysis and ELISA validation. DIA serum proteomic revealed that apolipoprotein C-I (APOC1), apolipoprotein D (APOD), and apolipoprotein A-IV (APOA4) were decreased. The reductases glutathione S-transferase omega-1 (GSTO1) and peptidyl-prolyl cis-trans isomerase A (PPIA) were upregulated, and ADAMTS-like protein 4 (ADAMTSL4) was downregulated in both ischemic and hemorrhagic MMD. Afamin (AFM) and transforming growth factor-beta-induced protein ig-h3 (TGFBI) increased in ischemic patients but decreased in hemorrhagic patients. Serum ELISA results confirmed that APOA4, APOC1, and APOD were decreased compared to controls. Then, we retrospectively analyzed biochemical indexes of 200 MMD patients. A total of 54 enrolled MMD patients showed decreased total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-c). APOA4, APOC1, and APOD were vital factors in the HDL decrease in MMD patients. Lipoprotein dysfunction in MMD patients is involved in MMD. Intimal thickening by enhanced adhesion, middle layer vascular smooth muscle cell migration, and decreased lipid antioxidant function represented by HDL are potential pathogeneses of vascular changes in MMD.

Segmented carotid endarterectomy for treatment of Riles type 1A common carotid artery occlusion.

OBJECTIVE: Common carotid artery occlusion (CCAO) is a rare cause of cerebrovascular events. Symptomatic lesions are resistant to medical treatment and revascularization is often required, but there is no consensus on the treatment of CCAO at present. Riles type 1A CCAO is most likely to benefit from revascularization because it has patent outflow tract (internal carotid artery) which was supplied by patent external carotid artery (ECA) from collateral circulation. We described a novel surgical technique improved on the basis of the carotid endarterectomy (CEA) for treatment of Riles type 1A CCAO. METHODS: We rigorously screened ten patients with symptomatic Riles type1A CCAO for surgery from January 2017 to May 2019 and performed a full preoperative assessment of the inadequate collateral circulation compensation. Moreover, we retrospectively reviewed our experience of the segmented CEA in the treatment of them in our single center. RESULTS: Segmented CEA was performed on the left side in four cases and on the right side in six cases. The technical success rate of the procedure was 100%. Primary suture was used in nine cases. Only one patient (right CCAO) who had a history of neck radiotherapy was treated by the patch CEA. The mean temporary blocking time during surgery was 52.8 ± 9.15 min. The mean temporary blocking time for treating the upper segment of the common carotid artery (CCA) was 11.1 ± 2.64 min. In the postoperative period, cerebral perfusion on the ipsilateral site improved in all patients, myocardial infarction occurred in one patient, and recurrent laryngeal nerve damage occurred in another. No ischemic events or re-occlusion or restenosis (> 50%) of the treated CCA occurred during the mean follow-up of 32.6 ± 9.3 months. The preoperative mean modified Rankin Scale (mRS) score was 1.9 (range, 1-3; median, 2). At last follow-up for all patients, the mRS score was 1 (range, 0-3; median, 1). CONCLUSION: Segmented CEA, which utilizes the compensatory effect of collateral circulation, is an effective and safe technique to treat patients suffering from Riles type 1A CCAO with hemodynamic cerebrovascular compromise.

Evaluation of Revascularization in Different Suzuki Stages of Ischemic Moyamoya Disease by Whole-Brain CT Perfusion.

Objective: This study compared the clinical features and hemodynamic characteristics of patients in different Suzuki stages of ischemic moyamoya disease (iMMD) before and after treatment with extracranial-intracranial (EC-IC) bypass surgery combined with encephalo-duro-myo-synangiosis and whole-brain computed tomography perfusion (WB-CTP). Methods: A total of 126 patients in different Suzuki stages (II, III, IV, and V) of iMMD who underwent bypass surgery from April 2013 to August 2020 were included in this retrospective study. MIStar automatic analysis of Whole brain CT perfusion imaging software (WB-CTP, Apollo Medical Imaging Technology, Melbourne, Australia) was used. The patients also underwent WB-CTP 1 day before and 1 week and 3 months after the surgery. The relationships between hemodynamic parameters in WB-CTP including delay time (DT) > 3 s, relative cerebral blood flow (rCBF) < 30%, mismatch and mismatch ratio, and clinical outcomes were evaluated for different Suzuki stages, with comparisons between early (II and III) and late (IV and V) stages. Results: Combined bypass surgery was performed in 161 hemispheres of 126 patients with iMMD. Brain volume with DT > 3 s was decreased 1 week (51.5 ± 11.8 ml, P < 0.05) and 3 months (41.5 ± 10.7 ml, P < 0.05) after bypass compared to 1 day before bypass (104.7 ± 15.1 ml) in early-stage patients. In late-stage patients, the volume was increased 1 week after bypass compared to the preoperative value (154.3 ± 14.7 vs. 118.3 ± 19.1 ml, P < 0.05). Preoperative brain volume with rCBF < 30% was lower (9.8 ± 3.9 vs. 33.5 ± 11.0 ml) whereas preoperative mismatch ratio was higher (11.2 ± 2.8 vs. 3.6 ± 1.6) in early-stage as compared to late-stage patients (both P < 0.05). A higher modified Rankin scale score (0-1) was achieved by early-stage patients than by those in the late stage (93.8 vs. 80.4%, P < 0.05) at the 3-month follow-up. Conclusions: WB-CTP is useful for assessing the effectiveness of combined bypass/revascularization in different Suzuki stages of iMMD. Patients in the early stage of disease with higher preoperative brain volume with DT > 3 s and mismatch ratio show greater improvements in hemodynamic parameters and fewer postoperative complications associated with hemodynamic disturbance following bypass than patients in the late stage. Preoperative mismatch ratio can serve as a marker for assessing the status of collateral circulation in different Suzuki stages of iMMD.

Assessment of Transient Cerebral Hemodynamic Disturbance via Whole-Brain Computed Tomography Perfusion After Extracranial-Intracranial Bypass in Ischemic Moyamoya Disease.

OBJECTIVE: To assess the cerebral hemodynamic data associated with transient cerebral hemodynamic disturbance (TCHD), including cerebral hyperperfusion syndrome (CHS) and watershed shift ischemia (WSI), by whole-brain (WB) computed tomography perfusion (CTP) before and after revascularization for ischemic moyamoya disease. METHODS: A total of 115 consecutive patients with ischemic moyamoya disease underwent revascularization. All patients underwent WB-CTP 24 hours before operation and on the day of onset of TCHD and 6 months after revascularization. The volumes of delay time (DT) >3 seconds and mismatch and relative cerebral blood flow <30% were calculated in 3 time points. RESULTS: Of the 115 patients, 18 115 had TCHD, comprising 10 with CHS and 8 with WSI. Compared with the brain volume of DT >3 seconds before revascularization, the volume decreased significantly (P < 0.05) on the day of CHS. The volume of mismatch in 3 time points indicated no significant differences (P > 0.05). The volume of relative cerebral blood flow <30% showed obvious differences of significance among 10 patients with CHS (P < 0.05) at 3 time points. In the WSI group, the volume of DT >3 seconds, mismatch, and DT >3 seconds showed significant differences, relatively (P < 0.05), at 3 time points. At the time of onset of TCHD, DT >3 seconds and mismatch in the CHS group were dramatically lower than those in the WSI group (P < 0.05). DT >3 seconds in the no-TCHD group showed significant differences (P < 0.05) at 3 time points. CONCLUSIONS: WB-CTP could be used to assess the cerebral hemodynamic characteristics before and after revascularization. DT >3 seconds and mismatch played important roles in evaluating distinct features of TCHD.

Quantitative analysis of revascularization in ischemic moyamoya disease via whole-brain computed tomography perfusion: A retrospective single-center study.

Ischemic moyamoya disease (MMD) can be treated with the revascularization of superficial temporal artery to middle cerebral artery (STA-MCA) bypass combined with encephalo-duro-arterio-myo-synangiosis (EDAMS) effectively. The purpose of the present study was to quantify the revascularization of STA-MCA bypass combined with EDAMS via whole-brain computed tomography perfusion (WB-CTP).Seventy-nine consecutive patients with ischemic MMD who admitted to our hospital from August 2012 to October 2018 were carried out STA-MCA bypass combined with EDAMS. WB-CTP was performed at 24 hours prior to operation and 3 months following bypass with a follow-up WB-CTP, respectively. Both automatic analysis of WB-CTP (MIStar, Apollo Medical imaging Technology, Melbourne, Australia) for analyzing values of brain volume in delayed time (DT) >3 seconds and DT > 6 seconds, relative cerebral blood flow (γCBF) < 30% and its mismatch ratio or percentage and diffusion-weighted imaging of magnetic resonance imaging in the ischemic penumbra and the infarct core at the 2 time points were studied for verifying the effectiveness of the combined revascularization. Changes in DT values at MCA-terminal territory after revascularization had been investigated. The dynamic data were with reference to the individual cerebellar arteries.All patients with ischemic MMD underwent STA-MCA bypass combined with EDAMS successfully. The preoperative brain volume in DT > 3 seconds in MCA-terminal territory was significantly larger than that of postoperative one (P < .05) in the ischemic penumbra in ischemic MMD. The mismatch ratio in brain volume of 24 hours prior to revascularization in MCA-terminal territory was significantly lower than that of 3 months (P < .05) following combined revascularization. The percentage of mismatch in brain volume of 24 hours prior to revascularization vs that of 3 months and the value of γCBF < 30% were similar to the above mismatch ratio (P < .05). The ratio of postoperative brain volume in DT > 3 seconds vs DT > 6 seconds indicated no significant differences compared with that of preoperative one (P > .05).The WB-CTP can be regarded as a choice for quantifying the combined revascularization in the ischemic penumbra and the infarct core in ischemic MMD. As proposed methods, brain volume in DT > 3 seconds, the value of γCBF < 30% and mismatch ratio in brain volume in MCA-terminal territory should be paid more attention in assessing the validity of STA-MCA bypass combined with EDAMS in ischemic MMD.

Surgical Revascularization: Ligation of Extracranial Internal Carotid Artery and Superficial Temporal Artery-to-Middle Cerebral Artery Bypass in Patient with Extracranial Internal Carotid Aneurysm and Hemorrhagic Moyamoya Disease.

BACKGROUND: Extracranial internal carotid artery (EICA) aneurysm is regarded as a rare lesion. What is more, patients can suffer from EICA aneurysms and hemorrhagic moyamoya disease (MMD) simultaneously. CASE DESCRIPTION: A 38-year-old man was admitted to our hospital and underwent emergent tracheal intubation for hoarseness and breathing difficulty for 1 day. He had a pulsating mass of 2.5 cm in diameter in the left cervical area. Imaging examinations revealed the left EICA aneurysm and MMD. The patient underwent left superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass and ligation of the left EICA simultaneously. Computed tomography revealed hemorrhagic stroke in the right basal ganglia region 20 days after the bypass. The hematoma disappeared 20 days after the stroke. Right bypass was performed 6 months after the left bypass. The patient was discharged with no neurologic abnormalities 10 days after the right bypass. He lived a normal life, and no neurologic abnormalities were found at the 6-month follow-up. Imaging examinations indicated the efficacy of the bilateral STA-MCA bypass and verified the disappearance of the left EICA aneurysm after the ligation. CONCLUSIONS: We present a case of EICA aneurysm and hemorrhagic MMD. Ligation of the left ECA eliminates the EICA aneurysm with no neurologic abnormalities. STA-MCA bypass can be regarded as an effective choice for hemorrhagic MMD. Further studies should be performed to confirm the effectiveness of combined surgical revascularization.

Extracranial-intracranial bypass in medial sphenoid ridge meningioma associated with severe stenosis of the intracranial segments of the internal carotid artery: A case report.

RATIONALE: Tumor resection and extracranial-intracranial bypass concerning medial sphenoid ridge meningioma associated with severe stenosis of the internal carotid artery (ICA) of intracranial segments has been rarely presented. Effective treatment as to the complex lesions may be complicated. Tumor resection and cerebrovascular protection should be both taken into consideration. PATIENT CONCERNS: We presented one case of medial sphenoid ridge meningioma associated with severe stenosis of the internal carotid artery of intracranial segments. The patient suffered hyperthyroidism, mirror-image dextrocardia and congenital heart disease atrial septal defect simultaneously. DIAGNOSES: Before the neurosurgical treatment , the colleagues of department of cardiac surgery, anesthesiology and respiratory medicine agreed on our plan of resecting the tumor following the comprehensive evaluation of basal clinical conditions in the patient. For reducing the bleeding intraoperatively, the interventional branch performed digital subtraction angiography(DSA) and found collateral anastomosis between the supplying vessels of left middle meningeal arteries and anterior choroid arteries. No preoperative interventional embolization was determined considering the risk of cerebral ischemia. INTERVENTIONS: The following subtotal resection of medial sphenoid ridge meningioma and left extracranial-intracranial bypass were carried out. Additionally, ipsilateral decompressive craniectomy was done. Post-operative imaging Computed tomography (CT), Computed tomography angiography (CTA) and Transcranial Doppler (TCD) indicated subtotal resection of tumor and bypass patency. OUTCOMES: The patient was discharged with the right limbs of muscle strength of grade IV. The muscle strength of the patient returned to grade V after 6 months of follow-up. LESSONS: Comprehensive treatment of tumor resection and extracranial-intracranial bypass concerning medial sphenoid ridge meningioma associated with severe stenosis of the internal carotid artery of intracranial segments is effective.

Disappearance of Ruptured Posterior Cerebral Artery Aneurysm Associated with Internal Carotid Artery Occlusion After Superficial Temporal Artery-to-Middle Cerebral Artery Bypass.

BACKGROUND: Internal carotid artery (ICA) occlusion associated with posterior cerebral artery (PCA) aneurysms is regarded as a rare cerebrovascular disease. Common treatment of aneurysms-direct clipping or coiling-is not taken into consideration for this kind of cerebrovascular property. Combined surgical cerebrovascular reconstruction of the superficial temporal artery-to-middle cerebral artery (STA-MCA) bypass offers a chance to downregulate the hemodynamic stress of aneurysm rupture. CASE DESCRIPTION: A 46-year-old female presented with a fever and headache 1 month ago. An axial computed tomography scan showed a subarachnoid hemorrhage (SAH). Digital subtraction angiography (DSA) was conducted, and the patient received an STA-MCA bypass following medical treatment for 1 month in the local hospital. Computed tomography angiography and DSA demonstrated an aneurysm located on the right PCA and an occlusion of the right ICA in our hospital. Three days after admission, the right STA-MCA bypass was performed. The patient suffered no neurologic deterioration and lived a normal life. 6 months after the STA-MCA bypass, DSA of the right vertebral artery revealed disappearance of the aneurysm located on the right PCA (P2 segment). CONCLUSIONS: Owing to ICA occlusion, the gap of hemodynamic stress between the posterior segment of the circle of Willis and anterior segment of the circle of Willis enlarged. This may lead to a ruptured PCA aneurysm. In this case, the aneurysm disappeared following an STA-MCA bypass. STA-MCA bypass may be one of the major reasons downregulating the gap, which can be regarded as an effective option concerning such aneurysms.

A comparative study of intraventricular central neurocytomas and extraventricular neurocytomas.

Similar histology and clinical behavior of both intraventricular central neurocytomas (CNs) and extraventricular neurocytomas (EVNs) may argue against the idea that EVNs were the distinct entity to distinguish from CNs in the 2007 World Health Organization classification. To explore respective characteristics and compare similarities and differences in CNs and EVNs, relevant clinical, radiological, operative and pathological data of 49 patients (35 CNs and 14 EVNs) in the Department of Neurosurgery at our hospital from 2005 to 2012 was reviewed and some comparisons between CNs and EVNs were conducted. The factors affecting posttreatment recurrence of CNs and EVNs were assessed by Cox regression analysis. In comparison, CNs showed a more typical clinical manifestation, and radiological and histopathological features, while EVNs demonstrated more malignant biological behavior, with higher MIB-1 index (p = 0.006), higher rate of atypia (p = 0.042), higher recurrence rate (p = 0.028), and shorter time to recurrence (p = 0.049). Subtotal resection was associated with higher rates of recurrence in both CNs (hazard ratio [HR] 6.16, p = 0.046) and EVNs (HR 5.26, p = 0.045), and atypia was also associated with a higher recurrence rate in CNs (HR 5.03, p = 0.042). CNs were thus easier to diagnose than EVNs, with typical clinical, radiological, and histopathological features, while the latter were more likely to show malignant biological behavior associated with atypia and recurrence. Total surgical resection is the optimal treatment choice for both CNs and EVNs, and patients with either CN or EVN with typical and/or totally resected lesions showed favorable clinical outcomes.

DCPIB, a potent volume-regulated anion channel antagonist, attenuates microglia-mediated inflammatory response and neuronal injury following focal cerebral ischemia.

Accumulating evidence indicates that extensive microglia activation-mediated local inflammation contributes to neuronal injury in cerebral ischemia. We have previously shown that 4-(2-butyl-6, 7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid (DCPIB), a potent volume-regulated anion channel (VRAC) inhibitor, suppresses pathological glutamate release and excitatory neurotoxicity in reversible middle cerebral artery occlusion (rMCAO) model in vivo. In the present study, we sought to determine whether DCPIB also attenuates microglia activation that could contribute to neuronal injury in the cerebral ischemia/reperfusion pathology. We show that oxygen-glucose deprivation (OGD) induced microglia proliferation, migration, and secretion of cytokines and all these pathological changes were effectively inhibited by DCPIB in vitro. In the microglia/neuron co-cultures, OGD induced neuronal damage was reduced markedly in the presence of DCPIB. In rat rMCAO animal model, DCPIB significantly attenuated microglia activation and neuronal death. Activation of mitogen-activated protein kinase (MAPK) signaling pathway is known to be a critical signaling pathway for microglia activation. We further explored a potential involvement of DCPIB in this pathway by western blot analysis. Under the conditions that MAPK pathway was activated either by lipopolysaccharides (LPS) or OGD, the levels of phosphorylated ERK1/2, JNK and p38 were reduced significantly in the presence of DCPIB. Altogether, our study demonstrated that DCPIB inhibits microglia activation potently under ischemic conditions both in vitro and in vivo. The DCPIB effect is likely attributable to both direct inhibition VRAC and indirect inhibition of MAPK pathway in microglia that are beneficial for the survival of neurons in cerebral ischemic conditions.

A treatment option for severe cerebellar hemorrhage with ventricular extension in elderly patients: intraventricular fibrinolysis.

External ventricular drainage (EVD) combined with intraventricular fibrinolysis (IVF) is rarely used in severe spontaneous cerebellar hemorrhage (SCH) with intraventricular hemorrhage (IVH). Recently, the treatment strategy was repeatedly performed in our hospital to elderly patients with severe SCH + IVH. To analyze its clinical value, we compared it to two treatment strategies which now commonly are used for these patients: conservative management (CM) and clot evacuation (CE). In this study, a total of 118 cases were observed, of which 28 cases received CM, 43 cases received EVD + IVF and 47 cases received CE. The Glasgow Coma Scale score, frequency of complication, mortality in one month, modified Rankin Scale (mRS) at six months, and causes of death were analyzed. The outcomes of patients in the CM group were extremely poor compared to patients undergoing surgery (P = 0.034) and the mortality was up to 61.3 % (18/28), which was much higher than those of the two surgical groups (P = 0.026). No significant difference was found in mortality and mRS between the two surgical groups (P > 0.05). Patients in the CE group mostly died of deterioration of comorbidities and postoperative complications, whereas more deaths occurred in the CM group and the EVD + IVF group due to rebleeding, brainstem compression, perilesional edema and tight posterior fossa (χ (2), P = 0.006). It is suggested that EVD + IVF is a treatment option for elderly patients with severe SCH + IVH.

[Compliance of the patients and related influential factors on the topical antifungal treatment of onychomycosis].

OBJECTIVE: To explore the compliance rate of patients and its influential factors on topical antifungal treatment of onychomycosis. METHODS: Dermatology life quality index (DLQI) and self-administered questionnaires were employed in this study. RESULTS: The overall compliance rate of the topical antifungal treatment was 23.9% (92/385). The cure rates on onychomycosis in patients with good compliance was 63.04% (58/92), but only 2.05% (6/293) in those noncompliant patients, respectively. Regarding the influencing factors as age, sex, level of awareness, occupation, course of disease, personal income, inconvenience in access to the treatment, keep forgetting in taking the medicine, being impatient, lack of confidence, misunderstanding on topical as 'dirty' and the process of drug taking was troublesome, together with the quality of life were identified. There were significant differences between those compliant or noncompliant patients. For some factors as adverse effects of drug, number of affected nails, site of the disease, too busy in daily life, lack of related knowledge etc., no significant differences were found between the compliant or noncompliant patients. CONCLUSION: Our results showed that onychomycosis patients had poor compliance in topical antifungal treatment which significantly influencing the therapeutic effects. Age, sex, level of awareness on the disease, occupation, course of disease, personal income, inconvenience in receiving the treatment, forgetting to take the medicine, lack of patience, lack of confidence, different kinds of misunderstanding about the disease and quality of life etc. might affect the compliance rate of the disease.