Scopoletin Attenuates Intracerebral Hemorrhage-Induced Brain Injury and Improves Neurological Performance in Rats.

BACKGROUND: Among the hypertension-related complications, the onset of intracerebral hemorrhage (ICH) is a destructive stage and is the most disabling type of stroke that has the highest death rate. At present, there is no promising treatment for ICH. OBJECTIVES: The present investigation was aimed at evaluating the safeguarding effect of scopoletin against ICH-induced brain injury. METHODS: We used Wistar male rats and divided them into 4 groups. Group 1 served as control, group 2 was induced with ICH, group 3 served as scopoletin-pretreated ICH rats, and group 4 as scopoletin drug control. During the experimental period, neurobehavioral outcome, cerebral edema, and neuroinflammation parameters were evaluated using RT-PCR and other biochemical analyses. RESULTS: The rats that received scopoletin treatment demonstrated a significant attenuation in neurological deficits, neurodegeneration markers expression (TREM-1, SERPINE-1), and restored cerebral edema compared to ICH animals. On the other hand, an upsurge in inflammatory cytokines, for example, TNF-α, IL-13, IL-1ß, and IL-17, was observed in ICH rats and was reduced to the level near normalcy in the scopoletin-treated groups. CONCLUSION: Our investigations propose that the effectiveness of scopoletin in improving acute neurological function after ICH is promising, and this could be a lead molecule for the development of treatment plans in ICH treatment.

The effects of video based nursing education on perioperative anxiety and depression in patients with gastric cancer.

The purpose of this study was to determine the effect of video-based nursing education on perioperative anxiety and depression. A total of 128 patients scheduled for minimally invasive gastrectomy were randomly divided into intervention (n = 64) and control (n = 64) group. The. The anxiety and depression scores, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were assessed before the intervention, 1 h before surgery and 24 h after surgery. And the cortisol levels were measured before the intervention and 1 h before surgery. No significant difference was observed in baseline anxiety score, depression score, vital signs and cortisol level (P > 0.05). The anxiety level, depression level, SBP, DBP and HR of patients in intervention group was significantly lower than that in control group at 1 h before surgery and 24 hs after surgery (P < 0.05). The serum cortisol in the intervention group was also significantly lower than that in the control group 1 h before surgery (p < 0.001). Video-based nursing education was effective in decreasing the perioperative anxiety and depression of patients undergoing minimally invasive gastrectomy. It could also keep vital signs and serum cortisol levels in normal limits.

Genetic Relationship Between Endothelin-1 Gene Polymorphisms and Intracerebral Hemorrhage Among Chinese Han People.

BACKGROUND The goal of the present study was to determine whether endothelin-1 (EDN1) variants are associated with intracerebral hemorrhage (ICH) risk among Chinese Han people. MATERIAL AND METHODS The genotyping of EDN1 rs5370 and rs6458155 polymorphisms were conducted in 154 ICH patients and 168 healthy controls using polymerase chain reaction (PCR) and sequencing. Deviation for genotype frequencies in controls from Hardy-Weinberg equilibrium (HWE) was assessed. The genotype and allele distribution of EDN1 polymorphisms was checked via χ² test between 2 groups. Strength of the association between EDN1 polymorphisms and ICH risk is presented by odds ratio (OR) and 95% confidence interval (95% CI). RESULTS Genotype distribution for rs5370 and rs6458155 polymorphisms in the control group both conformed to HWE (P>0.05). Only CC genotype and C allele frequencies of rs6458155 between ICH patients and healthy individuals were significantly different (P=0.025; P=0.043), indicating rs64581255 is associated with increased ICH onset (OR=2.214, 95% CI=1.009-4.461; OR=1.389, 95% CI=1.010-1.910). When adjusted by confounding factors, the significant correlations still existed between 2 groups (P=0.028, adjusted OR=2.217, 95% CI=1.092-4.500; P=0.046, adjusted OR=1.386, 95% CI=1.005-1.910). CONCLUSIONS EDN1 rs64581aEDN1 rs6458155 polymorphism may be a risk factor of ICH among Chinese Han people.55 polymorphism may be a risk factor of ICH among Chinese Han people.

Decreased let-7b is associated with poor prognosis in glioma.

Abnormal expression of let-7b has been observed in many tumors, including glioma. However, the clinical significance of let-7b in glioma remained unclear. The aim of the study was to explore the correlation of let-7b expression with clinicopathological factors and prognosis in human glioma.Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to detect the relative expression of let-7b in glioma tissues. The association of let-7b expression with clinicopatholoigcal features of glioma patients was estimated using chi-square test. Overall survival curves were plotted using Kaplan-Meier method with log rank test. The prognosis analysis was performed using Cox regression model, and the results were shown as hazard ration (HR) with 95% confidence interval (CI).The relative expression of let-7b was significantly lower in glioma tissues than that in normal brain tissues (P < .001). Furthermore, let-7b level was closely correlated with World Health Organization (WHO) grade (P = .027) and Karnofsky performance score (KPS) (P = .018). Survival analysis indicated that glioma patients with low let-7b expression had significantly shorter overall survival time than those with high expression (log rank test, P < .001). Let-7b might be an independent prognostic biomarker for glioma (P < .001, HR = 2.415; 95% CI: 1.531-3.808).Let-7b may be a promising prognostic factor in glioma.

Comparison of the clinical efficacy of craniotomy and craniopuncture therapy for the early stage of moderate volume spontaneous intracerebral haemorrhage in basal ganglia: Using the CTA spot sign as an entry criterion.

OBJECTIVES: Surgical treatment is widely used for haematoma removal in spontaneous intracerebral haemorrhage (ICH) patients, but there is controversy about the selection of surgical methods. The CT angiography (CTA) spot sign has been proven to be a promising factor predicting haematoma expansion and is recommended as an entry criterion for haemostatic therapy in patients with ICH. This trial was designed to evaluate the clinical efficacy of two surgical methods (haematoma removal by craniotomy and craniopuncture combined with urokinase infusion) for patients in the early stage (≤6h from symptom onset) of spontaneous ICH with a moderate haematoma volume (30 ml - 60 ml). PATIENTS AND METHODS: From January 2012 to July 2017, 196 eligible patients treated in our institution were enrolled according to the inclusion criteria. The patients were divided into the CTA spot sign positive type and CTA spot sign negative type according to the presence or absence of the CTA spot sign. For each type, the patients were randomly assigned to two groups, i.e., the craniotomy group, in which patients underwent craniotomy with haematoma removal, and the craniopuncture group, in which patients underwent minimally invasive craniopuncture combined with urokinase infusion therapy. Neurological function was evaluated with the Scandinavian Stroke Scale (SSS) at day 14. The disability level and the activities of daily living were assessed using a modified Rankin Scale (mRS) and Barthel Index (BI) at day 90. Case fatalities were recorded at day 14 and 90. Complications were recorded during hospitalization. RESULTS: For the CTA spot sign positive type, the craniotomy group had a higher SSS than that in the craniopuncture group (P < 0.05) at day 14. The rebleeding rate was higher in the craniopuncture group than that in the craniotomy group (P < 0.05) during hospitalization. The craniotomy group had a lower mRS than that in the craniopuncture group (P < 0.01) and had a higher BI than that in the craniopuncture group (P < 0.05) at day 90. There was no statistically significant difference in the fatality rate between the two groups. For the CTA spot sign negative type, there were no significant differences in the SSS, mRS, BI, fatality rate and complication rate between the two groups. CONCLUSION: ICH can be divided into the CTA spot sign positive and negative type according to the presence or absence of the CTA spot sign. For the CTA spot sign positive type, patients can benefit from craniotomy with haematoma removal, which can reduce the postoperative rebleeding rate and improve the prognosis. For the CTA spot sign negative type, both craniotomy and craniopuncture are applicable. Considering simple procedure and minor surgical injury, craniopuncture can be a more reasonable choice.

The important role of positioning in nasogastric tube insertion in unconscious patients: A prospective, randomised, double-blind study.

AIMS AND OBJECTIVES: To investigate whether positioning the body in a lateral decubitus position will facilitate nasogastric tube insertion in unconscious patients. BACKGROUND: Inserting a nasogastric tube into unconscious patients can be challenging because these patients cannot cooperate with the operator. The piriform sinus and arytenoid cartilage are the most commonly reported impaction sites. However, we found that the first impaction site was the backward displaced tongue when inserting a nasogastric tube in unconscious patients who often exhibited glossoptosis. Performing an intubation in the lateral decubitus position could make this procedure easy. DESIGN: This prospective, double-blind, parallel, randomised controlled trial was conducted in Hengshui City, Hebei Province, China. METHODS: A total of 110 cases of unconscious patients were enrolled. The patients were randomly assigned to a conventional group (group C) or a lateral decubitus position group (group L). In group C, the nasogastric tube was inserted while the patients were in a supine position using the conventional technique, and in group L, the tube was inserted in a lateral decubitus position or further tilting the body to a prone decubitus position 20-30°. We discussed reasonable intubation methods in unconscious patients by comparing the success rate on first insertion, the overall success rate, the intubation time and the complication rates between the two groups. RESULTS: Group L had a higher success rate on first insertion and overall success rate than group C (p < .05). The intubation time in group L was shorter than that in group C (p < .001), and the complication rate in group L was lower than that in group C (p < .05). The differences were statistically significant. CONCLUSIONS: The backward displaced tongue blocks the pharyngeal passage. Nasogastric tube insertions in the lateral decubitus position are recommended in unconscious patients because of the higher success rate, reduced intubation time and lower complication rate. RELEVANCE TO CLINICAL PRACTICE: This study provides an effective method for nasogastric tube insertions in unconscious patients.

Hyperbaric-Oxygen Therapy Improves Survival and Functional Outcome of Acute Severe Intracerebral Hemorrhage.

BACKGROUND: Prognosis of spontaneous intracerebral hemorrhage (ICH) remains poor worldwide. AIMS OF THE STUDY: To investigate the effect and optimal protocol for hyperbaric-oxygen therapy (HBOT), and reduce incidence of upper gastrointestinal bleeding (UGIB) in ICH. METHODS: This prospective, randomized, controlled trial included 565 patients with acute severe ICH. Participants were randomly assigned to a sham-control group (Group A) and four intervention groups: Groups B and C with 2.0 atmospheres absolute (ATA) pressure and HBOT exposure for 60 or 90 sessions, respectively; and Groups D and E with 1.5 ATA for 60 or 90 sessions, respectively. All patients received emergency craniotomy with hematoma evacuation. Outcome measures were modified Barthel Index (MBI) and modified Rankin Scale (mRS) scores, mortality rates at follow-up six months. UGIB rates were assessed as potential side effect. RESULTS: In four intervention groups, MBI and mRS scores were all significantly improved, and mortality rates were all significantly decreased compared with Group A (all p < 0.005). UGIB rates were 39.25, 60.00, 64.49, 36.79, and 34.26% in Groups A, B, C, D, and E, respectively. UGIB rates in Groups B and C were significantly increased compared with Groups A, D and E (all p < 0.005). None of UGIB were clinically significant. CONCLUSIONS: HBOT significantly improves survival and functional outcomes of ICH. HBOT at 1.5 and 2.0 ATA had the same beneficial effect. A pressure of 1.5 ATA and 60 HBOT exposures represents an optimal protocol for HBOT. Further studies are needed to optimize the protocol per specific patient.

Inhibition of tumor vasculogenic mimicry and prolongation of host survival in highly aggressive gallbladder cancers by norcantharidin via blocking the ephrin type a receptor 2/focal adhesion kinase/paxillin signaling pathway.

Vasculogenic mimicry (VM) is a newly-defined tumor microcirculation pattern in highly aggressive malignant tumors. We recently reported tumor growth and VM formation of gallbladder cancers through the contribution of the ephrin type a receptor 2 (EphA2)/focal adhesion kinase (FAK)/Paxillin signaling pathways. In this study, we further investigated the anti-VM activity of norcantharidin (NCTD) as a VM inhibitor for gallbladder cancers and the underlying mechanisms. In vivo and in vitro experiments to determine the effects of NCTD on tumor growth, host survival, VM formation of GBC-SD nude mouse xenografts, and vasculogenic-like networks, malignant phenotypes i.e., proliferation, apoptosis, invasion and migration of GBC-SD cells. Expression of VM signaling-related markers EphA2, FAK and Paxillin in vivo and in vitro were examined by immunofluorescence, western blotting and real-time polymerase chain reaction (RT-PCR), respectively. The results showed that after treatment with NCTD, GBC-SD cells were unable to form VM structures when injecting into nude mouse, growth of the xenograft was inhibited and these observations were confirmed by facts that VM formation by three-dimensional (3-D) matrix, proliferation, apoptosis, invasion, migration of GBC-SD cells were affected; and survival time of the xenograft mice was prolonged. Furthermore, expression of EphA2, FAK and Paxillin proteins/mRNAs of the xenografts was downregulated. Thus, we concluded that NCTD has potential anti-VM activity against human gallbladder cancers; one of the underlying mechanisms may be via blocking the EphA2/FAK/Paxillin signaling pathway.

Norcantharidin inhibits tumor growth and vasculogenic mimicry of human gallbladder carcinomas by suppression of the PI3-K/MMPs/Ln-5γ2 signaling pathway.

BACKGROUND: Vasculogenic mimicry (VM) is a novel tumor blood supply in some highly aggressive malignant tumors. Recently, we reported VM existed in gallbladder carcinomas (GBCs) and the formation of the special passage through the activation of the PI3K/MMPs/Ln-5γ2 signaling pathway. GBC is a highly aggressive malignant tumor with disappointing treatments and a poor prognosis. Norcantharidin (NCTD) has shown to have multiple antitumor activities against GBCs, etc; however the exact mechanism is not thoroughly elucidated. In this study, we firstly investigated the anti-VM activity of NCTD as a VM inhibitor for GBCs and its underlying mechanisms. METHODS: In vitro and in vivo experiments to determine the effects of NCTD on proliferation, invasion, migration, VM formation, hemodynamic and tumor growth of GBC-SD cells and xenografts were respectively done by proliferation, invasion, migration assays, H&E staining and CD31-PAS double stainings, optic/electron microscopy, tumor assay, and dynamic micro-MRA. Further, immunohistochemistry, immunofluorescence, Western blotting and RT-PCR were respectively used to examine expression of VM signaling-related markers PI3-K, MMP-2, MT1-MMP and Ln-5γ2 in GBC-SD cells and xenografts in vitro and in vivo. RESULTS: After treatment with NCTD, proliferation, invasion, migration of GBC-SD cells were inhibited; GBC-SD cells and xenografts were unable to form VM-like structures; tumor center-VM region of the xenografts exhibited a decreased signal in intensity; then cell or xenograft growth was inhibited. Whereas all of untreated GBC-SD cells and xenografts formed VM-like structures with the same conditions; the xenograft center-VM region exhibited a gradually increased signal; and facilitated cell or xenograft growth. Furthermore, expression of MMP-2 and MT1-MMP products from sections/supernates of 3-D matrices and the xenografts, and expression of PI3-K, MMP-2, MM1-MMP and Ln-5γ2 proteins/mRNAs of the xenografts were all decreased in NCTD or TIMP-2 group; (all P < 0.01, vs. control group); NCTD down-regulated expression of these VM signaling-related markers in vitro and in vivo. CONCLUSIONS: NCTD inhibited tumor growth and VM of human GBCs in vitro and in vivo by suppression of the PI3-K/MMPs/Ln-5γ2 signaling pathway. It is firstly concluded that NCTD may be a potential anti-VM agent for human GBCs.

Contribution of the PI3K/MMPs/Ln-5γ2 and EphA2/FAK/Paxillin signaling pathways to tumor growth and vasculogenic mimicry of gallbladder carcinomas.

Vasculogenic mimicry (VM) is a new tumor blood supply in some highly aggressive malignant tumors. We previously reported VM in human gallbladder carcinomas, 3-D matrices in vitro and nude mouse xenografts in vivo of highly aggressive GBC-SD cells and its clinical significance. In this study, we further studied the underlying mechanisms of VM in gallbladder carcinomas via the 3-D matrix in vitro, the nude mouse xenografts in vivo of GBC-SD or SGC-996 cells, immunohistochemistry (H&E staining and CD31-PAS double staining), electron microscopy, expression of MMP-2, MT1-MMP, PI3K, Ln-5γ2, EphA2, FAK and Paxillin-P proteins/mRNAs determined by SABC, ELISA, immunofluorescence, western blotting and qRT-PCR, respectively. It was shown that all of untreated highly aggressive GBC-SD cells and xenografts formed vasculogenic-like structures within 2 weeks of seeding and injecting, and facilitated the growth of tumor cells or xenografts; whereas poorly aggressive SGC-996 cells or GBC-SD cells treated by TIMP-2 were unable to form the vasculogenic-like structures with the same conditions; and tumor xenograft growth was inhibited. Expression of MMP-2, MT1-MMP proteins/mRNAs from sections and supernates of 3-D matrix in vitro, expression of PI3K, MMP-2, MT1-MMP, Ln-5γ2, EphA2, FAK and Paxillin-P proteins/mRNAs from sections of xenografts in vivo in untreated GBC-SD group was upregulated significantly (all P<0.001); however, expression of these VM signal-related proteins/mRNAs in the SGC-996 group and GBC-SD treated by the TIMP-2 group was significantly downregulated (all P<0.001). Thus, we identified for the first time that highly aggressive GBC-SD cells formed VM in vitro and in vivo through the upregulation of PI3K/MMPs/Ln-5γ2 and/or EphA2/FAK/Paxillin signaling. PI3K/MMPs/Ln-5γ2 and EphA2/FAK/Paxillin as key signaling pathways in a coordinated manner contributed to tumor growth and VM of gallbladder carcinomas and provided novel targets that could be potentially exploited for therapeutic intervention of human gallbladder carcinomas.

[Vasculogenic mimicry in human primary gallbladder carcinoma and clinical significance thereof].

OBJECTIVE: To investigate if there is vasculogenic mimicry (VM) in human primary gallbladder carcinoma and clinical significance thereof. METHODS: Seventy-four specimens of primary gallbladder carcinoma obtained from operation underwent HE staining and double staining of CD(31) and PAS to observe the existence of VM. The correlation of pathological examination and clinical outcomes was analyzed. RESULTS: VM was seen in 10 of the 74 (13.5%) specimens. VM was not correlated with age, sex, location, diameter, differentiation degree, Nevin stage, and invasion depth of tumor, and existence of lymph node metastasis; but was associated with histological type (chi(2) = 10.241, P = 0.017), hepatic metastasis (chi(2) = 11.904, P = 0.01), and poor overall survival (chi(2) = 5.771, P = 0.016). Cox analysis showed that existence of VM, invasion depth, lymph node metastasis, hepatic metastasis, and operational method were independent risk factors of the prognosis of primary gallbladder carcinoma. CONCLUSION: VM exists in human primary gallbladder carcinoma. Those cases of human primary gallbladder carcinoma with VM have a poorer prognosis.