The natural course, treatment outcomes, and long-term prognosis of cervical spinal cord arteriovenous shunts.

OBJECTIVE: The highly intricate nature of the cervical spinal cord can cause arteriovenous shunts in these segments that may be associated with heightened clinical risks and treatment complexities. In this article, the authors aimed to provide a comprehensive analysis of the detailed natural course, treatment, and clinical outcomes of cervical spinal cord arteriovenous shunts (SCAVSs) based on the largest cohort to date. METHODS: Two hundred forty consecutive patients were included. Data on clinical presentation, angioarchitecture, treatment, and follow-up were retrospectively reviewed. RESULTS: The cohort demonstrated a greater prevalence of acute onset (63.3% vs 36.7%). Spontaneous recovery was observed in 63.7% of patients after onset, with a significantly elevated recovery rate observed among patients experiencing acute onset (72.4% vs 48.9%, p < 0.001). The risks of acute and gradual clinical deterioration after onset was 11.9%/year and 13.4%/year, respectively. Microsurgery was performed in 39.6% of patients, while the remaining 60.4% exclusively underwent embolization. The complete obliteration rate was 65.3% after microsurgery and 21.4% after embolization. The rate of treatment-related deterioration was 14.7% after microsurgery and 6.2% after embolization. After partial treatment, the acute and gradual deterioration rates were 4.1%/year and 6.6%/year, respectively. Lack of spontaneous recovery after onset was an independent predictor of embolization-related deterioration (OR 17.905, p = 0.007) and long-term gradual deterioration after partial treatment (HR 2.325, p = 0.021). After a median follow-up period of 32.55 months, prognosis was unfavorable in 16.7% of patients, with the sole independent risk factor being the absence of spontaneous recovery after onset (OR 2.476, p = 0.018). CONCLUSIONS: The outcomes of patients with cervical SCAVS were generally favorable, even in patients with only partial obliteration of the lesions. However, patients who did not show a trend toward spontaneous recovery after onset had a significantly elevated risk of unfavorable prognosis, highlighting the need for prompt clinical intervention.

Clinical Reasoning: A 49-Year-Old Woman With Isolated Sinus Intracranial Dural Arteriovenous Fistula With Perimedullary Drainage.

While demyelination is the most common etiology of longitudinally extensive myelopathy, other causes are important to recognize. In this study, we present the case of a longitudinal cervical lesion with a very rare cause. We discuss the approach to the differential diagnosis and workup for longitudinal myelopathy. This clinical reasoning case also illustrates the anatomical relationship between symptomatic spinal cord lesions and nonsymptomatic intracranial etiologies.

Health-related quality of life outcomes and influencing factors in patients with unruptured intracranial aneurysms after endovascular treatment.

BACKGROUND: Health-related quality of life (HRQoL) is an important indicator when evaluating prognosis and disease-related treatments. Our current knowledge of the HRQoL outcomes of unruptured intracranial aneurysm (UIA) patients treated by the endovascular intervention appeared to be very limited. To fill this gap, the present study investigated the HRQoL outcomes and identified the influencing factors in UIA patients treated by endovascular intervention. METHODS: We conducted a single-center cross-sectional study on patients who underwent endovascular treatment for UIAs. HRQoL outcomes were assessed by the 36-item Short Form Health Survey (SF-36). The SF-36 results of the Chinese reference population were used as the reference data. The independent variables with a univariate analysis result of P < 0.05 were included in the multivariate analysis. Finally, multivariable linear regression analysis was performed to identify the factors influencing HRQoL. Bonferroni correction was utilized for multiple testing correction. RESULTS: A total of 200 patients (83 males and 117 females, mean age of 55.2 ± 9.48 years) with UIAs treated by endovascular intervention were enrolled. The scores of SF-36 in 8 domains for UIA patients treated by endovascular intervention did not all reach the average level of the Chinese reference population after an average recovery period of 30.67 ± 8.6 months. Ischemic cerebrovascular disease history, advanced age, and mRS progression at discharge were independent risk factors of HRQoL for UIA patients treated by endovascular intervention, but physical exercise at least once a week and daily sleep time no < 6 h were independent protective factors. CONCLUSION: The HRQoL of UIA patients treated by the endovascular intervention was decreased to varying degrees compared with those of the Chinese reference population. The influencing factors of HRQoL explored by this study provide insights for improving the clinical management and daily lives of these patients. HRQoL assessment should be included in future aneurysm prognostic studies to provide better evidence.

Prevalence of and risk factors for anxiety and depression in Chinese patients with unruptured intracranial aneurysms treated by endovascular intervention.

BACKGROUND: Studies on anxiety and depression in unruptured intracranial aneurysm (UIA) patients after treatment via endovascular intervention are rare and controversial. We aimed to explore the prevalence of anxiety and depression among Chinese patients with UIAs treated by endovascular intervention and to identify which factors contribute to the development of these symptoms. METHODS: We performed a cross-sectional study on anxiety and depression in patients who underwent endovascular treatment for UIAs using the Hospital Anxiety and Depression Scale (HADS). The demographic, clinical and radiological data for all patients were retrospectively collected from the aneurysm database and medical records. Moreover, we utilized data from a large sample of 200 UIA patients and multivariate logistic regression analysis to investigate the risk factors for anxiety and depression in these patients. Candidate variables with P values less than 0.20 in univariate analysis were included in the multivariate logistic regression analysis. RESULTS: Two hundred patients returned completed questionnaires in this study. Of these 200 patients, 34 (17.0%) suffered from anxiety and 31 (15.5%) suffered from depression 30.67 ± 8.6 months after being discharged. The multivariate analysis results indicated that shorter sleep times were statistically significantly associated with depression (OR = 1.62, 95% CI: 1.14 ~ 2.29, P = 0.007, Adjusted P = 0.02). . CONCLUSION: The prevalences of anxiety and depression in UIA patients treated by endovascular intervention were 17.0 and 15.5%, respectively. Shorter sleep times were significantly associated with depression. Our findings provide evidence for the clinical and psychological management of these patients.

Using the modified Delphi method to research the influencing factors of long-term health-related quality of life in patients with unruptured intracranial aneurysms after endovascular treatment.

BACKGROUND: The purpose of this study was to use the modified Delphi method to identify the influencing factors of health-related quality of life (HRQoL) in patients with unruptured intracranial aneurysms (UIAs) after endovascular treatment. METHODS: A modified Delphi method to obtain expert consensus on the content of potential influencing factors of HRQoL in patients with UIAs treated by endovascular intervention was employed. The research team consists of three neuroradiologists and one epidemiologist from Xuanwu Hospital of Capital Medical University. They randomly selected 21 well-known experts in cerebrovascular disease diagnosis and treatment as participating experts. The importance of the indicator is based on the 5-Likert scale. The standard deviation (SD), coefficient of variation (CV), mean ( x ¯ ), and minimum and maximum scores of each indicator were calculated. The consistency was described by Kendall coefficient of concordance with a p value < 0.05 indicating that the expert consistency was high. RESULT: Twenty-one and 18 questionnaires were responded in 2 rounds, with effective response rates of 85.7% and 100.0%, respectively. The average authoritative coefficient (Cr) of all 21 experts was 0.88, familiarity with the indicators (Cs) was 0.82, and the judgment basis of the indicators (Ca) was 0.94. Eventually, the x ¯ values of arterial puncture hematoma, hyperlipidemia, gender, marital status, and hospitalization for other diseases were lower than 3.5; CV for marital status and gender was higher than 0.35. The Kendall coefficient of concordance in the first round was 0.19 (p < 0.001), and the second round was 0.15 (p < 0.001). CONCLUSION: In this study, the factors affecting the recovery of HRQoL after endovascular treatment in patients with UIAs were analyzed by the modified Delphi method, which provided a valuable evidence for the clinical management and daily life guidance for UIAs patients.

Microsurgical and Endovascular Treatment Outcomes in Pericallosal Artery Aneurysms: A Single Center Retrospective Analysis.

AIM: To summarize the clinical outcomes, follow-up results and to discuss the optimal therapeutic strategy for pericallosal artery aneurysms (PAAs). MATERIAL AND METHODS: From January 2013 to May 2017, the charts of 49 patients with PAAs, representing 2.43% of 2,018 consecutive patients with intracranial aneurysms (IAs) were reviewed. The clinical and radiological data of these patients were retrospectively analyzed. RESULTS: There were no technical failures in the clipping group, but one patient in the coiling group presented rebleeding during the operation, resulting in a poor prognosis. Although the difference was not significant, the coiling group had a better complete recovery rate than the clipping group [overall: coiling, n=20 (87.0%) vs clipping, n=11 (68.8%), p=0.33; unruptured PAAs: coiling, n=12 (92.3%) vs clipping, n=5 (83.3%); ruptured PAAs: coiling, n=8 (80%) vs clipping, n=6 (60%), p=0.63]. One patient in the coiling group exhibited recurrence. No patients experienced rebleeding during the follow-up period in either group. CONCLUSION: In our study, both endovascular coiling and microsurgery were technically feasible and achieved favorable clinical outcomes in patients with PAAs. Longer radiological follow-up is necessary. Patients should be evaluated by a multidisciplinary team prior to determining the optimal treatment modality.

Natural history of spinal cord arteriovenous shunts: an observational study.

The natural history of intradural spinal cord arteriovenous shunts is unknown. We performed an observational study in a consecutive patient cohort with symptomatic intradural spinal cord arteriovenous shunts who were admitted to three institutes to investigate the clinical course of this complex disease, which would provide valuable evidence to inform clinical decision-making. The clinical course of patients with symptomatic intradural spinal cord arteriovenous shunts from initial presentation to occurrence of clinical deterioration, initiation of treatment, or last follow-up was analysed. Patients with at least 1 month of observation were included in this study. Clinical onset and deterioration patterns were divided into acute and gradual. Annual and cumulative rates of clinical deterioration as well as their risk factors were analysed using Kaplan-Meier life table analysis and Cox proportional hazards model. To assess risks and benefits of treatment, post-treatment clinical courses were further assessed. Four hundred and sixty-six patients with a mean observational period of 36.9 ± 58.8 months were included; 56.7% of patients presented with acute onset, of whom 77.3% experienced spontaneous recovery. Age of onset older than 28 years, initial modified Aminoff and Logue scale of >3, mid-thoracic lesions and non-ventral lesions were independent predictors of failure for spontaneous recovery. The annual risk of general, acute and gradual clinical deterioration after onset was 30.7%, 9.9% and 17.7%, respectively. Risk of deterioration was highest in the early period after initial onset. Acute onset was the only independent risk factor [hazard ratio 1.957 (95% confidence interval, CI 1.324-2.894); P = 0.0008] of acute deterioration and gradual onset was the strongest predictor [hazard ratio 2.350 (95% CI 1.711-3.229); P < 0.0001] of the gradual deterioration among all the stratifying factors. After invasive treatment, complete obliteration was achieved in 37.9% of patients (138 of 364) and improved or stable clinical status was noted in 80.8% of patients. Forty-two patients (11.5%) experienced permanent complications. Overall post-treatment deterioration rate was 8.4%/year, and 5.3%/year if permanent complications were excluded. The natural history of symptomatic spinal cord arteriovenous shunts is poor, especially in the early period after onset, and early intervention is thus recommended. Initial onset pattern significantly affects the natural history of the lesion, which prompts a differentiated treatment strategy.

Filum Terminale Arteriovenous Fistulas with Multiple Shunt Points: A Report of Two Exceptional Cases.

BACKGROUND: Filum terminale arteriovenous fistula (FTAVF) with multiple shunt points has not been reported in the literature. In previous studies, the angioarchitecture of FTAVFs was always featured with only one single shunt point, and such a uniformity had established the preconceived and conventional understanding of FTAVFs for clinicians. CASE DESCRIPTION: The authors describe 2 exceptional cases of FTAVFs with multiple shunt points confirmed by open surgery, which means that the above understanding may lead to misdiagnosis and incomplete treatment in future. The surgery of both cases was performed in a hybrid operating room, and all of shunt points were obliterated with the help of intraoperative digital subtraction angiography. CONCLUSIONS: The exceptional finding of these 2 cases is a renewal of the conventional understanding of FTAVFs, not only for the angioarchitecture of the lesions but also for the treatment strategy.

Identification of cow milk in goat milk by nonlinear chemical fingerprint technique.

The objective of this paper was to develop a nonlinear chemical fingerprint technique for identifying and detecting adulteration of goat milk with cow milk. In this study, by taking the Belousov-Zhabotinsky oscillatory chemical reaction using acetone and substrates in goat milk or cow milk as main dissipative substances, when the same dosage of goat milk and cow milk was introduced to the "H+ + Mn2+ + BrO3- + acetone" oscillating system respectively, nonlinear chemical fingerprints were obtained for goat milk and cow milk from the same origin. The results showed that inductive time value and the content of cow milk in goat milk had a linear relationship in the range of 0-100% and the corresponding regression coefficient was 0.9991. A detection limit of 0.0107 g/g was obtained, and the content of cow milk in mixed milk was calculated. The proposed method in this study was simple, economical and effective. In addition, the method did not need the pretreatment and separation of samples for identifying and evaluating cow milk adulteration in goat milk.

Pediatric thoracic SCIWORA after back bend during dance practice: a retrospective case series and analysis of trauma mechanisms.

PURPOSE: The purpose of the study was to describe a unique type of low-energy traumatic pediatric thoracic spinal cord injury without radiographic abnormality (SCIWORA) after a back bend during dance practice and analyze the trauma mechanisms and treatment protocols. METHODS: This was a retrospective case series from September 2007 to August 2016. The study was conducted at a tertiary medical center in Beijing, China (Xuanwu Hospital, China International Neuroscience Institute [China-INI], Capital Medical University). A total of 12 pediatric patients who had a clear traumatic history after back bend movements and had been diagnosed with thoracic SCIWORA were included. Clinical and imaging data were obtained for each patient. The follow-up data was analyzed. The traumatic mechanisms were investigated by analyzing the patients' medical history, spinal diffusion tensor imaging (DTI) and fiber tractography data. RESULTS: Of the 12 patients, 11 (91.7%) were younger than 8 years old. The mean age of the patients was 6.6 years. All patients had a clear traumatic history of severe thoracic spinal cord injury after performing back bend movements. The mean follow-up time was 36.5 months. During the follow-up period, 1 patient (8.3%) recovered completely, and 11 patients (91.7%) had unfavorable prognoses, including 4 (33.3%) with incomplete recovery and 7 (58.3%) with no change. Two patients underwent spinal DTI, which showed rupture of the nerve fiber bundle in the section of the injury. CONCLUSIONS: Back bend movements performed during dance practice may cause pediatric thoracic SCIWORA, particularly in children younger than 8 years old. We suggest that the mechanism of primary injury is the longitudinal distraction of the thoracic spine during back bend movements, which leads to violent distraction of the spinal cord and blunt injury of nerve axons, nerve cells, and small vessels. Spinal DTI may facilitate the diagnosis and prognostic evaluation of SCIWORA.

A New Type of Spinal Epidural Arteriovenous Fistulas Causes Spinal Epidural Hemorrhage: An Analysis of Five Cases and Natural History Consideration.

BACKGROUND: Spinal epidural arteriovenous fistulas (SEDAVFs) are peculiar and poorly understood lesions with a poorly understood natural history. They usually are subclassified into 2 types according to their drainage components. This study aimed to describe a new type of SEDAVFs that is featured with a unique drainage pattern and present our natural history hypothesis of SEDAVFs. METHODS: Five SEDAVF cases of the new type were reviewed retrospectively from a high case-volume spinal vascular malformation database. The clinical manifestations, neuroradiologic findings, angioarchitecture, treatment strategies, and clinical outcomes were assessed. RESULTS: All patients presented with spontaneous spinal epidural hematoma, and 2 of them exhibited rebleeding. The median age at the initial episode was 20 years. Spinal digital subtraction angiography revealed slow-flow epidural fistulas drained by spinal epidural venous plexus without intradural drainage or engorged venous pouches in all 5 patients. Three patients underwent microsurgical treatment. The outcomes of all of the patients were favorable. CONCLUSIONS: Our study reported a special type of hemorrhagic SEDAVF without an intradural drainage component or epidural mass effect. The key diagnostic clue was early opacification of spinal epidural venous plexus on spinal angiogram. We believe SEDAVFs may form at an early age and gradually develop with time. Different types of SEDAVFs may represent different developing stages of one disease, and our type may represent the early stage of SEDAVFs.

Spontaneous Spinal Epidural Hematoma: A Study of 55 Cases Focused on the Etiology and Treatment Strategy.

BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is a rare neurologic emergency of the spinal cord. Its cause and treatment strategy remain controversial. This study aimed to evaluate a significant cause of SSEH and to discuss the treatment strategy according to the clinical outcomes of patients in 2 institutions. METHODS: Fifty-five cases of SSEH treated at our institutions between February 2002 and February 2016 were retrospectively analyzed. RESULTS: The mean age of the first SSEH onset was 31.8 years. The follow-up rate was 72.7%, with 28 patients (70%) showing satisfactory clinical outcomes. Forty patients received preoperative spinal digital subtraction angiography. Spinal epidural (extradural) arteriovenous fistula was detected in 6 patients (15%), 5 of whom showed 1 type of special slow-flow shunt. Nineteen patients (34.5%) suffered from multiple episodes until they underwent invasive treatments or last follow-up. Rebleeding was confirmed in 8 patients. None of the patients had a subsequent episode or rebleeding after invasive treatment. The risk factors for poor clinical outcome included advanced age at initial onset (P = 0.020), a short progression interval (P = 0.030), no symptom relief after admission (P = 0.011), hypesthesia (P = 0.017), complete spinal cord injury (P = 0.001), and hematoma below the T4 level (P = 0.014). CONCLUSIONS: Spinal epidural (extradural) arteriovenous fistula is a significant cause of SSEH. Standard spinal digital subtraction angiography is necessary for patients with SSEH. Conservative treatment could not prevent occurrence of multiple episodes or rebleeding in patients. Microsurgery should be recommended as the preferred treatment strategy for SSEH. Endovascular embolization is also recommended if applicable.

[Robo1 expression in non-small cell lung cancer and its brain metastasis].

OBJECTIVE: To detect the expression of Robo1 in lung cancer tissues, adjacent non-cancerous tissues as well as lung cancer brain metastasis, and explore the correlation of Robo1 expression to lung cancer brain metastasis. METHODS: SP (streptavidin-peroxidase) staining method was used to examine the Robo1 expression in specimens from 80 cases of NSCLC, 52 cases of adjacent non-cancerous tissues and 72 cases of lung cancer with single brain metastasis (without metastasis in other organs). The Robo1 expression was further examined in 17 self control cases with lung cancer tissues and their brain metastasis tissues. The results were assessed by Kaplan-Meier analysis and log-rank test. RESULTS: The positive expression rate of Robo1 among adjacent non-cancerous tissues, lung cancers tissues and the lung cancer brain metastasis tissues were 1.9% (1/52), 13.8% (11/80) and 40.3% (29/72), respectively, and significant differences were detected among them (P < 0.05). During the 17 self control cases, the positive expression rate of Robo1 in lung cancer tissue and their brain metastasis tissues were 17.6% and 64.7%, respectively, with a significant difference between them (P < 0.01). Among the 72 cases of lung cancer brain metastasis, the median survival time of cases with positive Robo1 expression was 10 months, significantly shorter than that of cases with negative expression of Robo1 (17 months, P < 0.05). CONCLUSIONS: The positive expression rate of Robo1 was increased in sequence from the lowest in adjacent non-cancerous tissues, intermediate in the lung cancer tissues to highest in the lung cancer brain metastasis tissues. The expression of Robo1 in lung cancer brain metastasis is negatively correlated with the prognosis of patients with lung cancer brain metastasis. Robo1 may promote the genesis and progression of lung cancer and lung cancer brain metastasis as a cancer-promoting oncogene.

[Cytoplasmic expression of aquaporin-1 in breast cancer cells and its relationship with clinicopathological characteristics and prognosis].

OBJECTIVE: To detect the expression of aquaporin 1 (AQP1) in breast cancer tissues, and to analyze its relationship with clinicopathological characteristics and prognosis of breast cancer patients. METHODS: Histochemical SP staining was used to assess the AQP1 expression in 30 cases of lobular hyperplasia of mammary gland, 16 cases of ductal carcinoma in situ (DCIS), and 78 cases of invasive ductal carcinoma-not otherwise specified (IDC-NOS), and to analyze the relationship between cytoplasmic expression of AQP1 in IDC-NOS and clinical pathological characteristics and prognosis of the patients. RESULTS: Positive AQP1 immunolabelling appeared as brown deposit over the membrane of myoepithelial cells in all cases of lobular hyperplasia of mammary gland, but only 10.0% of cases showed cytoplasmic staining in glandular epithelial cells. In the ductal carcinoma in situ, brown deposit of AQP1 immunolabelling appeared over the myoepithelial cell membrane in all cases, but only 12.5% of cases were accompanied with cytoplasmic staining in glandular epithelial cells. In the invasive ductal carcinoma not otherwise specified, 35.9% of the cases showed cytoplasmic AQP1 immunoreactivity, but only 3.8% of cases showed positive membrane staining of the tumor cells. There were highly positive AQP1 expression in 14 cases, weakly positive in 14 cases, and negative in 50 cases. Cytoplasmic AQP1 expression in the IDC-NOS cases was significantly correlated with pathologic stage, PR, HER-2, lymph node status, Nottingham prognostic index (NPI) and metastasis or recurrence (all P < 0.05). The 5-year progression-free survival (PFS) rates were 16.8% in the patients with strong positive AQP1 expression, 90.9% in the cases with weakly positive AQP1 expression and 94.9% in the AQP1-negative cases, showing a significant difference (P < 0.05). Multivariate analysis indicated that the lymph node status and cytoplasmic expression of AQP1 were independent factors for PFS (both P < 0.05). The 5-year overall survival (OS) rates were 45.6% in the AQP1- strong positive cases, 90.0% in the AQP1-weakly positive cases and 97.7% in the AQP1-negative cases, showing a significant difference (P < 0.05). Multivariate analysis indicated that the lymph node status and cytoplasmic expression of AQP1 were independent factors affecting the overall survival and progression-free survival (both P < 0.05). CONCLUSION: AQP1 is mainly expressed on the membrane of myoepithelial cells in the benign breast lesions, but in the cytoplasm of breast cancer cells, and its expression is an independent factor affecting prognosis of breast cancer patients.

[Function of intersectin in endocytosis and exocytosis].

Intersectin is an evolutionarily conserved multifunctional adaptor protein with multifunctional domains. These domains interact with components of the endocytic and exocytic pathways, such as the clathrin mediating synaptic vesicle recycling, the protein related to endocytosis via caveolae, the with-no-lysine kinases related to the regulation of renal outer medullar potassium, and the Cdc42 mediating exocytic pathway. Recently, the understanding of intersectin function in the pathogenesis of endocrine tumor and many neurodegenerative diseases such as Down syndrome, Alzheimer disease has been deepened. This article reviewed the structure and roles in endocytosis/exocytosis and diseases of intersectin.

[Expression and significance of phosphorylated Girdin in breast cancer].

OBJECTIVE: To detect the expression of phosphorylated girdin (p-girdin) in breast cancer and its association with pathological characteristics and molecular subtypes of breast cancer. METHODS: Immunohistochemical SP staining was used to investigate the expression of p-girdin in 27 cases of lobular hyperplasia of mammary gland, 61 cases of ductal carcinoma in situ (DCIS), and 94 cases of non-special type invasive carcinoma (IDC-NOS) of breast. RESULTS: p-girdin was located in the cell cytoplasm and (or) nuclei in breast cancer. There was statistically a very significant difference among lobular hyperplasia, DCIS and IDC-NOS (χ2=26.724, P<0.001). Its cytoplasmic and nuclear reactivity were 25.9% (7/27), 39.3% (24/61), and 66.0% (62/94), respectively. The expression of p-girdin was positively associated with pathologic stage (r=0.204, P=0.049), lymph node metastasis (r=0.212, P=0.041) and HER2/neu (r=0.248, P=0.016). But no significant association was identified between p-girdin expression and histological grade (r=-0.015, P=0.918), age of patients (r=-0.011, P=0.918), tumor size (r=0.075, P=0.471), ER(r=0.071, P=0.498), PR (r=-0.050, P=0.634). Mann-Whitney test showed that p-girdin expression in luminal A, luminal B, triple negative and HER-2(+) type was significantly different (χ2=14.017, P=0.003). Among the four types, its positive rate was 55.8% (24/43), 95.8% (23/24), 66.7% (10/15), and 41.7% (5/12), respectively. CONCLUSIONS: p-Girdin expression is closely correlated with the malignant progression of breast cancer. Its expression may have clinical value as a new target for the treatment of breast cancer.

[Expression of Notch1, MMP-2 and MMP-9 and their significance in glioma patients].

OBJECTIVE: To study the expression of Notch1, MMP-2 and MMP-9 in glioma patients and their relationship with progression and prognosis of gliomas. METHODS: Sixty-four cases of glioma were included in this study. There were four cases of grade 1 tumor, twenty-five cases of grade 2, nine cases of grade 3, and twenty-six cases of grade 4. Immunohistochemistry (SP staining method) was used to detect the expression of Notch1, MMP-2 and MMP-9 in glioma tissues and adjacent non-tumor tissues, and the patients were followed up. RESULTS: Notch1, MMP-2 and MMP-9 were detected in glioma tissues but not in adjacent non-tumor tissues. The expression of Notch1 was increased with the pathological grade of the gliomas (r = 0.262, P < 0.05). The survival time of patients with strong expression of Notch1 was 31.0 months, significantly shorter than that of patients with non-strong positive (negative, weak and moderately) Notch1 expression (53.0 months, P < 0.05). Significant difference in survival time was observed between patients with negative and positive expression of MMP-9 (P < 0.05). CONCLUSIONS: Notch1, MMP-2 and MMP-9 are closely correlated with the progression and prognosis of malignant gliomas. Notch1 may participate in the expression regulation of MMP-2 and MMP-9. Compared with MMP-2, MMP-9 may play a more important role in determining the prognosis of malignant glioma. Notch1 and MMP-9 may become new biological markers for prognosis of patients with malignant glioma.

Cellular microRNA let-7c inhibits M1 protein expression of the H1N1 influenza A virus in infected human lung epithelial cells.

The influenza virus (IV) triggers a series of signalling events inside host cells and induces complex cellular responses. Studies have suggested that host factors play an essential role in IV replication. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that target mRNAs, triggering either translation repression or RNA degradation. Emerging research suggests that host-derived cellular miRNAs are involved in mediating the host-IV interaction. Using miRNA microarrays, we identified several miRNAs aberrantly expressed in IV-infected human lung epithelial cells (A549). Specifically, miR-let-7c was highly up-regulated in IV-infected A549 cells. PITA and miRanda database screening indicated that the let-7c seed sequence is a perfect complementary sequence match to the 3' untranslated region (UTR) of viral gene M1 (+) cRNA, but not to PB2 and PA. As detected by a luciferase reporter system, let-7c directly targeted the 3'-UTR of M1 (+) cRNA, but not PB2 and PA. To experimentally identify the function of cellular let-7c, precursor let-7c was transfected into A549 cells. Let-7c down-regulated IV M1 expression at both the (+) cRNA and protein levels. Furthermore, transfection with a let-7c inhibitor enhanced the expression of M1. Therefore, let-7c may reduce IV replication by degrading M1 (+) cRNA. This is the first report indicating that cellular miRNA regulates IV replication through the degradation of viral gene (+) cRNA by matching the 3'-UTR of the viral cRNA. These findings suggest that let-7c plays a role in protecting host cells from the virus in addition to its known cellular functions.

Protocatechuic aldehyde inhibits lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis via regulation of caspase-3.

Apoptosis of vascular endothelial cells results in the loss of endothelial integrity, and is a risk factor of atherosclerosis (AS). Lipopolysaccharide (LPS) stimulates inflammation during AS. The current study examined the effect of a potent water-soluble antioxidant, protocatechuic aldehyde (PCA; derived from the Chinese herb Salvia miltiorrhiza) on apoptosis in human umbilical vein endothelial cells (HUVECs) stimulated with LPS. The LPS (15 µg/ml) stimulation for 30 h resulted in significant HUVEC apoptosis, as detected by Hoechst 33258 staining and Annexin V analysis. The PCA (0.25-1.0 mmol/L, 12 h) inhibited LPS-induced HUVEC apoptosis in a dose-dependent manner. Lipopolysaccharide induced caspase-3 activation, but had no significant effect on caspase-2, Bcl-2/Bax, cytochrome c, caspase-9 and granzyme B expression. Protocatechuic aldehyde (0.25-1.0 mmol/L) significantly inhibited caspase-3 activation in a dose-dependent manner. A specific caspase-3 inhibitor also protected against LPS-induced apoptosis; however, no cooperative effect of PCA and the inhibitor was observed in this study. Collectively, these results indicate that PCA inhibits LPS-induced apoptosis in HUVECs through a mechanism that involves caspase-3.