Combining therapy with recombinant human endostatin and cytotoxic agents for recurrent disseminated glioblastoma: a retrospective study.

BACKGROUND: The optimal chemotherapeutics of recurrent disseminated glioblastoma has yet to be determined. We analyzed the efficacy and safety of recombinant human endostatin (rh-ES) combined with temozolomide and irinotecan in patients with recurrent disseminated glioblastoma. METHODS: We retrospectively reviewed 30 adult patients with recurrent disseminated glioblastoma treated with this combination chemotherapy at Department of Neuro-Oncology, Sanbo Brain Hospital, Capital Medical University of China from November 2009 to August 2018. Temozolomide was given orally at 200 mg/m2 daily for 5 days and rh-ES was administrated 15 mg/d daily for 14 days of each 28-day treatment cycle. Irinotecan was given intravenously every 2 weeks on a 28-day cycle at 340 mg/m2 or 125 mg/m2 depending on antiepileptic drugs. Primary endpoint was progression-free survival (PFS) at 6 months (6 m-PFS). RESULTS: The 6 m-PFS was 23.3%. The median PFS was 3.2 months. The overall survival rate (OS) at 12 months was 28.6%. The median OS was 6.9 months. Six out of 30 (20%) patients demonstrated partial radiographic response and 11 (36.7%) remained stable. The PFS of the 6 patients who got partial response was 5.8, 6.3, 6.9, 13.6, 15.8 and 16.6 months, respectively, and the median time interval of first response was 4 (range, 2.0-6.6) months. The most common adverse events were hematologic toxicities and gastrointestinal effects. The Grade ≥ 3 adverse event was hematologic toxicities. The adverse events were manageable. CONCLUSIONS: Rh-ES, in combination with cytotoxic drugs, was an alternative effective regimen with manageable toxicities in treatment of recurrent disseminated glioblastoma.

The clinical assessment of amyotrophic lateral sclerosis patients' prognosis by ZNF512B gene, neck flexor muscle power score and body mass index (BMI).

BACKGROUND: Assessment on the prognosis of amyotrophic lateral sclerosis (ALS) is becoming a focus of research in recent years since there is no effective treatment. The aim of the research is to explore the major factors involving in prognosis of ALS patients through long-term follow-up. METHODS: ALS patients' DNA extracted from peripheral blood white cells were detected for the risk allele by single nucleotide polymorphism (SNP) analysis. Neck flexor muscle score and body mass index (BMI) were recorded during Medical Research Council follow-up using manual muscle testing method. RESULTS: ALS patients with risk alleles (C) deteriorated rapidly with poor clinical outcome. It seemed that the higher neck flexor muscle strength score in ALS patients with the longer survival time but without significant correlation (p > 0.05). The lower the basal body mass index, the shorter the survival time and the faster deterioration (p < 0.05). The patients with body mass index less than 22.04 seemed to have short survival time than those with BMI more than 22.04 (p < 0.05), however, the speed of deterioration in two groups of patients had no significant difference (p > 0.05). CONCLUSION: The risk (C) allele of the SNP (rs2275294) in the ZNF512B gene, cervical flexor muscle power and body weight index might have clinical potential for ALS prognostication, since these indicators is so simple to perform that they might be very suitable for primary clinics and even community medical institutions to carry out.

[Effects of Qizhi Jiangtang capsule on protein expressions of InsR, PI3K, GLUT2 and p-JNK in hepatic tissues of rats with type 2 diabetes].

To observe the hypoglycemic effect of Qizhi Jiangtang capsule in rats with type 2 diabetes, and investigate the preliminary mechanism of its hypoglycemic effect, type 2 diabetes rat models were established by high glucose and high fat combined with small dose of streptozotocin (STZ). After continuous administration for 6 weeks, blood glucose, and glycosylated serum protein (GSP) levels were detected in all of the animals; immunohistochemistry assay was used to detect the number of islet ß cells; Western blot assay was used to detect the protein expression levels of insulin receptor (InsR), phosphoinositide-3 kinases (PI3K), glucose transporter-2 (GLUT2) and phosphorylated Jun N-terminal kinases (p-JNK)in hepatic tissues. The results showed that Qizhi Jiangtang capsule could reduce the blood sugar and GSP levels in serum in animals with type 2 diabetes mellitus, increase the level of insulin in serum and number of islet ß cells, increase the protein expression levels of InsR, PI3K and GLUT2, and reduce the level of p-JNK protein expression. In conclusion, Qizhi Jiangtang capsule has relatively stable hypoglycemic effect, and the mechanism may be associated with increasing the number of islet ß cells and level of insulin in serum, up-regulating the protein expression levels of InsR, PI3K and GLUT2, down-regulating the level of p-JNK protein expression in hepatic tissues, and reducing the level of insulin in hepatic tissues.

[Effects of Qizhi Jiangtang capsule on dermal ulcer in type 2 diabetic rats].

The effect of Qizhi Jiangtang vapsule (QJC) on degree of dermal ulcer cicatrization in 2 type diabetic rats was studied. Except the rats for blank group, other male Wistar rats were used to establish type 2 diabetic model by feeding with high sugar and high fat diet for four weeks and intraperitonally injecting with 30 mg•kg⁻¹ streptozotocin (STZ). After that, the rats were divided into balanced groups according to blood sugar, and received corresponding drugs for treatment for 8 weeks. At the end of week 8, 2 cm diameter circular incision was done on the back of rats. After that, the rats were administered continuously for10 days. Area of ulcer surface was detected every two days. After the last administration, wound granulation tissues were cut down to conduct pathological examination and detect the expression of VEGF, PI3K, p-ERK protein in wound tissues. The results showed that compared with the model group, after application of Qizhi Jiangtang capsule (2.24 g•kg⁻¹), the wound was significantly reduced on day 6 and day 10 of wound formation; inflammation reaction on ulcer surface was significantly reduce; Qizhi Jiangtang capsule can increase VEGF expression in the wound tissues of diabetic rats, and inhibit ERK phosphorylation. It can be concluded that Qizhi Jiangtang capsule can promote skin ulcer healing for diabetes rats, and its mechanism may be related to regulating the expression of VEGA and p-ERK proteins.

BACE1 RNA interference improves spatial memory and attenuates Aß burden in a streptozotocin-induced tau hyperphosphorylated rat model.

Both senile plaques and intracellular neurofibrillary tangles are important pathological characteristics in Alzheimer's disease. However, the relationship between Aß deposition and tau hyperphosphorylation is unknown. In this study, the increased levels of full-length amyloid precursor protein (APP), APP C-terminal fragment (ß-CTF) and BACE1 were found in streptozotocin-induced tau hyperphosphorylation models by quantitative polymerase chain reaction, Western blotting and immunohistochemistry methods. In the previous studies, few strategies focusing on inhibiting ß-secretase (BACE1) in a tau hyperphosphorylation model were utilized. Here, BACE1 RNAi was used to treat the streptozotocin-induced tau hyperphosphorylation animal models. BACE1 RNAi treatment improved the behavioural ability of animal models and reduced the amount of Aß1-40 and Aß1-42, accompanied by decreasing the levels of BACE1 and ß-CTF. Our results demonstrated that neurological defects and neurotoxic fragments, including Aß and ß-CTF, were eliminated by BACE1 RNAi in the tau hyperphosphorylated model, implying the efficiency and safety of BACE1RNAi treatment against Alzheimer's disease.

[Treatment of stage 3b diabetic kidney disease patients with macroalbuminuria by qizhi jiangtang capsule: a multicenter randomized control clinical study].

OBJECTIVE: To observe the efficacy and safety of Qizhi Jiangtang Capsule (QJC) in treating stage 3b diabetic kidney disease (DKD) patients with macroalbuminuria. METHODS: Patients who conformed to the diagnostic criteria of stage 3b DKD were randomly assigned to two groups according to random digital table, the experiment group and the control group, 84 in each group. All patients received a two-week elution period, and then were treated with basic Western therapy. Patients in the experiment group took QJC, 5 pills per time, 3 times a day, while those in the control group took Valsartan Capsule 160 mg each time, once daily. The observation period of follow-ups was limited within 6 months, and the time points were set as the baseline, 1st month, 3rd month, and 6th month. Systolic blood pressure (SBP), diastolic blood pressure (DBS), 24 h urine protein quantitative (24 h UPQ), plasma albumin (ALB), and serum creatinine (SCr) were detected and recorded, and estimated glomerular filtration rate (eGFR) was calculated. The occurrence of hypoglycemic reaction, coagulation disorder, gastrointestinal tract reaction, allergy, hyperkalemia, doubling of creatinine, and overall adverse events were observed and recorded at same time. RESULTS: Finally 81 patients in the experiment group and 80 patients in the control group were effectively included. Compared with the baseline level, SBP and DBS obviously decreased in the control group at month 1 of treatment (P < 0.05), and more significantly decreased at month 6 of treatment (P < 0.01). SBP at month 1, 3, and 6 of follow-ups; DBS at month 6 of follow-ups was lower in the control group than in the experiment group (P < 0.05). At month 1, 3, and 6 of follow-ups, 24 h UPQ of the experiment group was significantly lower than the baseline level (P < 0.01). It was also significantly lower than the level of the control group at the same time point (P < 0.05). There was no significant difference in 24 h UPQ at month 1, 3, and 6 of follow-ups between the control group and the baseline level (P > 0.05). ALB of the experiment group showed an increasing trend. It was significantly higher than the baseline level at month 6 (P < 0.05), which was also higher than that of the control group at same period (P < 0.05). There was no significant difference in the ALB level in the control group (P > 0.05). SCr of two groups showed an increasing trend. SCr of the experiment group was significantly higher at month 1, 3, and 6 follow-ups than the baseline level (P < 0.05). But the increment of SCr was higher in the control group than in the experimental group, and obviously higher than the baseline levels (P < 0.05). eGFR of both groups showed a decreasing trend. The decrement was higher in the control group than in the experimental group (P < 0.05). The proportion of progression of renal functions at month 1, 3, and 6 of follow-ups in the experimental group was 0.0% (0 case), 9.55% (8 cases), and 21.4% (18 cases), while they were 8.3% (7 cases), 21.4% (18 cases), and 40.5% (34 cases) in the control group. There was no statistical difference in the proportion of progression of renal functions between the two groups at month 3 and 6 of follow-ups (P < 0.05). There was no statistical difference in the incidence of adverse reactions between two groups (P > 0.05). CONCLUSION: QJC could effectively reduce urinary protein of patients with stage 3b DKD, and delay the progression of renal functions.

Comprehensive analysis and molecular map of Hippo signaling pathway in lower grade glioma: the perspective toward immune microenvironment and prognosis.

Background: The activation of YAP/TAZ transcriptional co-activators, downstream effectors of the Hippo/YAP pathway, is commonly observed in human cancers, promoting tumor growth and invasion. The aim of this study was to use machine learning models and molecular map based on the Hippo/YAP pathway to explore the prognosis, immune microenvironment and therapeutic regimen of patients with lower grade glioma (LGG). Methods: SW1783 and SW1088 cell lines were used as in vitro models for LGG, and the cell viability of the XMU-MP-1 (a small molecule inhibitor of the Hippo signaling pathway) treated group was evaluated using a Cell Counting Kit-8 (CCK-8). Univariate Cox analysis on 19 Hippo/YAP pathway related genes (HPRGs) was performed to identify 16 HPRGs that exhibited significant prognostic value in meta cohort. Consensus clustering algorithm was used to classify the meta cohort into three molecular subtypes associated with Hippo/YAP Pathway activation profiles. The Hippo/YAP pathway's potential for guiding therapeutic interventions was also investigated by evaluating the efficacy of small molecule inhibitors. Finally, a composite machine learning models was used to predict individual patients' survival risk profiles and the Hippo/YAP pathway status. Results: The findings showed that XMU-MP-1 significantly enhanced the proliferation of LGG cells. Different Hippo/YAP Pathway activation profiles were associated with different prognostic and clinical features. The immune scores of subtype B were dominated by MDSC and Treg cells, which are known to have immunosuppressive effects. Gene Set Variation Analysis (GSVA) indicated that subtypes B with a poor prognosis exhibited decreased propanoate metabolic activity and suppressed Hippo pathway signaling. Subtype B had the lowest IC50 value, indicating sensitivity to drugs that target the Hippo/YAP pathway. Finally, the random forest tree model predicted the Hippo/YAP pathway status in patients with different survival risk profiles. Conclusions: This study demonstrates the significance of the Hippo/YAP pathway in predicting the prognosis of patients with LGG. The different Hippo/YAP Pathway activation profiles associated with different prognostic and clinical features suggest the potential for personalized treatments.

Migfilin sensitizes cisplatin-induced apoptosis in human glioma cells in vitro.

AIM: Filamin binding LIM protein 1, also known as migfilin, is a skeleton organization protein that binds to mitogen-inducible gene 2 at cell-extracellular matrix adhesions. The aim of this study was to investigate the role of migfilin in cisplatin-induced apoptosis in human glioma cells, to determine the functional domains of migfilin, and to elucidate the molecular mechanisms underlying the regulation of cisplatin-related chemosensitivity. METHODS: The human glioma cell lines Hs683, H4, and U-87 MG were transfected with pEGFP-C2-migfilin to elevate the expression level of migfilin. RNA interference was used to reduce the expression of migfilin. To determine the functional domains of migfilin, U-87 MG cells were transfected with plasmids of migfilin deletion mutants. After treatment with cisplatin (40 µmol/L) for 24 h, the cell viability was assessed using the MTS assay, and the cell apoptotic was examined using the DAPI staining assay and TUNEL analysis. Expression levels of apoptosis-related proteins were detected by Western blot analysis. RESULTS: Overexpression of migfilin significantly enhanced cisplatin-induced apoptosis in Hs683, H4, and U-87 MG cells, whereas downregulation of migfilin expression inhibited the chemosensitivity of these cell lines. The N-terminal region of migfilin alone was able to enhance the cisplatin-induced apoptosis. However, despite the existence of the N-terminal region, mutants of migfilin with any one of three LIM domains deleted led to a function loss. Furthermore, apoptotic proteins (PARP and caspase-3) and the anti-apoptotic protein Bcl-xL were modulated by the expression level of migfilin in combination with cisplatin. CONCLUSION: The LIM1-3 domains of migfilin play a key role in sensitizing glioma cells to cisplatin-induced apoptosis through regulation of apoptosis-related proteins.

[Experiences of transcallosal-interforniceal approach for resection of the third ventricle and the pineal region tumors: report of 24 cases].

OBJECTIVE: To discuss the advantages and disadvantages of transcallosal-interforniceal approach for resection of the third ventricle and the pineal region tumors. METHODS: The clinical data of 24 cases from July 2008 to March 2011 were retrospectively analyzed. All 24 patients operated by transcallosal-interforniceal approach, among them, there were 14 males and 10 females, with a average age of 32 years ranged from 17 to 65 years and with medical history from 1 month to 10 years. Issues of managements were analyzed and discussed, including reasonable incision design, the managements of draining vein, the site and the length of the incision of the corpus callosum, tumor exposure in increased intracranial pressure, prevention of complications, skills of surgery, treatments of obstructive hydrocephalus, and postoperative managements. RESULTS: In the 24 cases, there were 5 cases of pineal parenchymal tumors, 4 cases of germinoma, 3 cases of astrocytoma, 2 cases of hypothalamus hamartomas, 2 cases of ependymoma, 2 cases of mixed germ cell tumour, 2 cases of malignant lymphomas, 1 case of pineoblastoma, 1 case of dermoid cyst, 1 case of chordoid glioma and 1 case of craniopharyngioma. After surgeries, total removal achieved in 9 cases, and subtotal removal in 10 cases and partial removal in 5 cases. Operative mortality was 0. Combined third ventriculostomy were performed in 13 cases. Postoperative complications occurred in 5 cases, including frontoparietal epidural hematoma in 1 case; postoperative short-term memory loss in 3 cases, postoperative memory loss within 1 month in 2 cases and within 3 months in 1 case; frontoparietal subdural effusion in 1 case and the effusion disappeared without any treatment. Ventriculoperitoneal shunt was performed in 1 case. CONCLUSIONS: The transcallosal-interforniceal approach is ideal for the removal of tumors in third ventricle as well as majority tumor in posterior of third ventricle in a skillful hand. Tumor resection combined with third ventriculostomy is the significant advantages in the approach.

[Preliminary study on aberrant expression of miRNAs related to the formation of the distinction between pediatric and adult types of brainstem gliomas].

OBJECTIVES: To study the different expression of miRNA between pediatric and adult types of brainstem gliomas, and to provide the target miRNAs for explore the mechanism and miRNA interference of the malignant progression of pediatric BSG. METHODS: miRNA expression profiles in orthotopic models which could simulate the BSG heterogeneity were examined by microarray and analyzed to obtain the aberrantly expressed miRNAs. The two types of human BSG tissue were utilized to verify the microarray data by qRT-PCR and in situ hybridization for the putative causative miRNAs. RESULTS: There were 216 miRNAs detected in both the pediatric BSG group and the adult BSG group, 39 miRNAs to be differential expressed in the pediatric BSG group versus adult group, including 10 up-regulated and 29 down-regulated. qRT-PCR and in situ hybridization indicated good consistency with that of the microarray method. CONCLUSIONS: Aberrantly expressed miRNA may serve as putative causative involvement of malignant progression of pediatric BSG, thereby might be potentially novel targets for therapy.

Granulocyte colony-stimulating factor increases the therapeutic efficacy of bone marrow mononuclear cell transplantation in cerebral ischemia in mice.

BACKGROUND: Bone marrow mononuclear cell (BMMC) transplantation is a promising therapy for cerebral ischemia; however, little is known if its therapeutic efficacy may be improved by co-administration of potential modulatory factors in vivo. To explore this possibility, the present study examined the effect of BMMCs and G-CSF on cell proliferation, early neuronal development and neurological function recovery in experimental cerebral ischemia relative to controls that received neither treatment. RESULT: Ischemia/infarct area was significantly reduced in BMMCs+G-CSF group relative to animal groups treated with BMMCs only, G-CSF only or saline. Transplanted BMMCs were found to colocalize with the proliferative cell nuclear antigen (PCNA) and the immature neuronal marker doublecortin (DCX). The BMMCs+G-CSF group showed increased numerical density of cells expressing PCNA and DCX, improved performance in adhesive sticker removal test and reduced neurological function severity scores relative to other groups in a time-dependent manner. CONCLUSION: BMMCs and G-CSF co-administration exhibits synergistic beneficial effect over time. This effect could be at least partially related to increased proliferation and differentiation of bone marrow stem cells and enhanced host brain regeneration and functional recovery. The results suggest that G-CSF can increase the therapeutic efficacy of BMMCs transplantation in an experimental mouse model of cerebral ischemia.

Rosiglitazone protects neuroblastoma cells against advanced glycation end products-induced injury.

AIM: To investigate the protective effects of rosiglitazone (RGZ) against the neuronal toxicity induced by advanced glycation end products (AGEs) and the underlying mechanisms. METHODS: Neuroblastoma cell line SH-SY5Y was used. Cell viability and apoptosis were assessed using MTT assay and flow cytometry, respectively. Superoxide dismutase (SOD) and catalase activities were measured using biochemical methods. Intracellular reactive oxygen species (ROS) were monitored using 2',7'-dichlorodihydro-fluorescein diacetate (DCFH-DA). Secreted ß-amyloid(1-42) (Aß(1-42)) level was assessed by ELISA. The expression of mRNA of Bcl2, Bax, Caspase3, Aß precursor protein (APP), ß-site APP-cleaving enzyme 1 (BACE1), and insulin degrading enzyme (IDE) were measured using quantitative real-time PCR (Q-PCR), and their protein levels were examined using Western blot. RESULTS: RGZ (0.1-10 µmol/L) significantly increased the cell viability that was reduced by AGEs (1000 µg/mL). RGZ (10 µmol/L) significantly ameliorated AGEs-triggered downregulation of SOD and catalase, and production of ROS. It also reversed Bcl2 downregulation, Bax upregulation and Caspase3 expression caused by AGEs. Moreover, it significantly attenuated AGEs-induced Aß secretion and APP protein upregulation. RGZ did not affect BACE1 expression, but induced IDE expression, which promoted degradation of Aß. All the effects were blocked by the specific PPARγ antagonist GW9662 (10 µmol/L). CONCLUSION: RGZ protects the euroblastoma cells against AGEs-induced injury via its anti-oxidative, anti-apoptotic and anti-inflammatory properties that seems to be mediated by PPARγ activation. The results suggest a beneficial role for RGZ in the treatment of Alzheimer's disease.

[Microanatomic and three-dimensional reconstruction study of lateral wall and related structures of optic canal].

OBJECTIVE: To investigate the key microanatomic and radiological structures of optic canal comprehensively so as to provide anatomic parameters and procedural flows for the decompression of optic canal. METHODS: Gross observations and microscopic measurements were applied on 10 (20 sides) formalin-treated cadaveric specimens and 15 (30 sides) adult skulls. Using multislice helical CT (computed tomography)-aided three-dimensional reconstruction in combination with direct anatomic measurement, the investigators dissected, photographed, measured and analyzed the shape of optic canal and analyze its anatomic relationship with the adjoining structures. RESULTS: Optic canal was formed by the superior, inferior, medial and external walls and distal proximal opening. The lateral wall of optic canal was formed by anterior clinoid process with a length of (9.87 ± 1.34) mm, a width of (11.66 ± 2.35) mm, a base thickness of (5.35 ± 1.07) mm and a middle thickness of (4.50 ± 1.06) mm. Optic strut separating the optic canal from the superior orbital fissure was located inferiorly. And the distance between the apex of anterior clinoid process and the middle of ICA (internal carotid artery) groove was (4.25 ± 2.30) mm. The CSF (cerebrospinal fluid) leakage and secondary injury of optic nerve and injury of ICA, ophthalmic artery might occur during the surgical procedures due to the variation of anterior clinoid process. The microanatomic figures and radiological measurements had a mean difference very close to each other at (0.08 - 0.48) mm. No statistical difference was found (P > 0.05). CONCLUSION: Optic nerve, ophthalmic artery and ICA may be exposed by a high-speed drilling of the lateral wall of optic canal. The drilling dissection of lateral wall plays a vital role during a successful optic canal decompression. Radiological measurement and three-dimensional reconstruction of skull base may be of great clinical significance in lesion visualization. And it helps to make a better choice of surgical approaches. The measurements provide valuable references for surgeons and researchers.

[TG-FTIR study on pyrolysis of wheat-straw with abundant CaO additives].

Biomass pyrolysis in presence of abundant CaO additives is a fundamental process prior to CaO sorption enhanced gasification in biomass-based zero emission system. In the present study, thermogravimetric Fourier transform infrared (TG-FTIR) analysis was adopted to examine the effects of CaO additives on the mass loss process and volatiles evolution of wheat-straw pyrolysis. Observations from TG and FTIR analyses simultaneously demonstrated a two-stage process for CaO catalyzed wheat-straw pyrolysis, different from the single stage process for pure wheat-straw pyrolysis. CaO additives could not only absorb the released CO2 but also reduce the yields of tar species such as toluene, phenol, and formic acid in the first stage, resulting in decreased mass loss and maximum mass loss rate in this stage with an increase in CaO addition. The second stage was attributed to the CaCO3 decomposition and the mass loss and maximum mass loss rate increased with increasing amount of CaO additives. The results of the present study demonstrated the great potential of CaO additives to capture CO2 and reduce tars yields in biomass-based zero emission system. The gasification temperature in the system should be lowered down to avoid CaCO3 decomposition.

Alterations in the RTK/Ras/PI3K/AKT pathway serve as potential biomarkers for immunotherapy outcome of diffuse gliomas.

BACKGROUND: Diffuse gliomas are the most common malignant brain tumors, and immune checkpoint inhibitors have limited therapeutic effects against this cancer. Three oncogenic pathways are altered in diffuse gliomas: the RTK/Ras/PI3K/AKT signaling, TP53, and RB pathways. Although these pathways may affect the tumor immune microenvironment, their association with immunotherapy biomarkers remains unclear. METHODS: We used copy number variation and mutation data to stratify patients with specific oncogenic signaling alterations, and evaluated their correlation with predictive immunotherapy biomarkers, including tumor mutation burden (TMB), immune cytolytic activity (CYT), tumor purity, and tumor-infiltrating CD8+ T cells. Immune checkpoint expression and interferon-γ signaling activity were also compared in these samples. RESULTS: We identified differentially expressed genes in three distinct oncogenic pathways. Gene ontology analysis of these genes revealed the involvement of RTK/Ras/PI3K/AKT-associated genes in immune and inflammatory responses. Moreover, significantly elevated TMB, CYT, and numbers of CD8+ T cells and decreased tumor purity were correlated with altered RTK/Ras/PI3K/AKT signaling. Single cell sequencing also confirmed that this tumor subgroup had increased immune checkpoint expression and interferon-γ signaling activity. Immune phenotyping based on the presence of CD274 and TMB or CD274 and CD8 T+ cells indicated that tumors with altered RTK/Ras/PI3K/AKT pathways represent a beneficial subtype and are associated with improved survival. CONCLUSION: Altered RTK/Ras/PI3K/AKT signaling and immunotherapy biomarkers are strongly correlated in gliomas. Gliomas with altered expression of RTK/Ras/PI3K/AKT pathway components may be sensitive to immunotherapy. A combination of small-molecule kinase inhibitors and immunotherapy is proposed for this subgroup of tumors.

Transplanted bone marrow stem cells relocate to infarct penumbra and co-express endogenous proliferative and immature neuronal markers in a mouse model of ischemic cerebral stroke.

BACKGROUND: Several studies demonstrate that neurogenesis may be induced or activated following vascular insults, which may be important for neuronal regeneration and functional recovery. Understanding the cellular mechanism underlying stroke-associated neurogenesis is of neurobiological as well as neurological/clinical relevance. The present study attempted to explore potential homing and early development of transplanted bone marrow stem cells in mouse forebrain after focal occlusion of the middle cerebral artery, an experimental model of ischemic stroke. RESULTS: Bone marrow stem cells isolated from donor mice were confirmed by analysis of surface antigen profile, and were pre-labeled with a lipophilic fluorescent dye PKH26, and subsequently transfused into recipient mice with middle cerebral artery coagulation. A large number of PKH26-labeled cells were detected surrounding the infarct site, most of which colocalized with immunolabelings for the proliferating cell nuclear antigen (PCNA) and some also colocalized with the immature neuronal marker doublecortin (DCX) during 1-2 weeks after the bone marrow cells transfusion. CONCLUSIONS: The present study shows that transplanted bone marrow cells largely relocate to the infarct penumbra in ischemic mouse cerebrum. These transplanted bone marrow cells appear to undergo a process of in situ proliferation and develop into putative cortical interneurons during the early phase of experimental vascular injury.

The role of GLP-1/GIP receptor agonists in Alzheimer's disease.

BACKGROUND: New glucagon-like peptide-1 (GLP-1) analogues developed in recent years have a long half-life and offer further prospects for clinical application. At present, the neuroprotection of GLP-1 analogues in Alzheimer's disease (AD) has just begun to be explored. OBJECTIVES: To investigate how glucagon-like peptide-1 (liraglutide) plays a protective role in AD by regulating tau activation and BACE1 expression. MATERIAL AND METHODS: Human neuroblastoma cell line SH-SY5Y cells were cultured in vitro and pretreated with different concentrations of liraglutide, and then treated with different concentrations of okadaic acid (OA) in order to observe the apoptosis of the SH-SY5Y cells. After liraglutide treatment, the apoptosis of neurons in AD rats was detected using flow cytometry, and tau activation and ß-site APP cleaving enzyme 1 (BACE1) expression were detected using western blot. RESULTS: Different concentrations of OA were able to induce apoptosis of SH-SY5Y cells in a dose-dependent manner. Different concentrations of liraglutide were used to pretreat SH-SY5Y cells, which were able to protect the SH-SY5Y cells from apoptosis induced by OA. Okadaic acid significantly increased tau activation and BACE1 expression in the SH-SY5Y cells, which was blocked with liraglutide pretreatment. The results of a water maze experiment showed that liraglutide had significant protective effects on memory and cognitive ability in AD rats induced with OA, inhibited apoptosis of neural cells in AD rats, and inhibited tau activation and BACE1 expression of neural cells in AD rats induced with OA. CONCLUSIONS: Liraglutide has a protective effect on AD in vivo and in vitro, which may be mediated by preventing neuronal apoptosis and inhibiting the activation of tau and the expression of BACE1.

[Effects of VCAM-1 siRNA on restenosis following carotid endarterectomy: experiment with rats].

OBJECTIVE: To evaluate the inhibitory effects of VCAM-1 siRNA on VCAM-1 protein expression and restenosis following carotid endarterectomy in rats. METHODS: Lentivirus-based VCAM-1 siRNA was constructed and its efficacy of blocking VCAM-1 protein expression in endothelial cells and carotids was identified by Western blot. Doppler ultrasonography and morphometric analysis were performed to measure the degree of restenosis. RESULTS: VCAM-1 siRNA decreased the protein expression of VCAM-1 in cultured endothelial cells and carotids. Treatment of VCAM-1 siRNA showed a significant reduction in the restenosis and manifested as an increased blood velocity and linear diameter as compared with control siRNA (P < 0.05). Morphometric analysis showed that the ratio of intima to media area (I/M) increased significantly in CEA group (3.99 +/- 0.65) versus sham-operated group (0.35 +/- 0.13) (P < 0.05). Furthermore, VCAM-1 siRNA resulted in an evident decrease in the neointimal area (1.79 +/- 0.43) as compared with that of the control siRNA (4.33 +/- 0.59) (P < 0.05). CONCLUSION: VCAM-1 plays an important role in pathogenesis of restenosis after carotid endarterectomy. VCAM-1 siRNA blocks VCAM-1 protein expression and alleviates the restenosis following carotid endarterectomy in rats.

[Outcomes of early surgery combined with anti-vasospasm agents treat ruptured cranial aneurysms: an analysis of 127 cases].

OBJECTIVE: Retrospective study on 127 cases of early microsurgery combined with antivasospasm agents for treatment of subarachnoid hemorrhage after the rupture of intracranial aneurysm. To evaluate the microsurgery for early-stage (3 days) of ruptured aneurysm. METHODS: 127 cases of subarachnoid hemorrhage after the rupture of intracranial aneurysm were diagnosed by MRI and CTA. Patients underwent early microsurgical clipping of intracranial aneurysm followed by antivasospasm agents treatment were retrospectively analyzed for their clinical manifestation, characteristics of imaging presentation, the curative effects and experiences of different operative approaches, surgical methods and techniques, pharmaceutical treatment and other integrated management. RESULTS: In all 127 cases, organized blood clot accompanied with subarachnoid hemorrhage and cerebral vasospasm surrounding the ruptured aneurysm was found in the course of surgical probing, among which 21 aneurysms ruptured during the operation; according to the GOS, 109 cases were cured or free of symptom, 23 cases got a transient hemiparalysis or aggravation of hemiparalysis, among which 18 cases were free of symptom, 9 were slight disability, 6 were severe disability, 3 cases die when discharged. CONCLUSIONS: Early operation could prevent second-time rupture effectively, lower the death rate, and at the same time lower the occurrence of cerebral vasospasm and the succeeding damage caused. Cerebral vasospasm is still the serious complication of subarachnoid hemorrhage of ruptured aneurysm and inappropriate management would cause critical consequences. Antivasospasm agents used postoperative could help preventing cerebral vasospasm and maintaining function.

[Treatment strategy of pituitary invasive prolactinomas].

OBJECTIVE: To discuss the treatment strategy of invasive prolactinomas (IPs) involving the cavernous sinus. METHODS: Data from 80 patients with IPs treated in our institutions were reviewed retrospectively. The criteria utilized included: (1) invasion of the cavernous sinus by tumor, corresponding to Grade III-IV according to the classification of Knosp; (2) serum prolactin level > 9.1 nmol/L; (3) clinical signs of hyperprolactinemia and mass effect. Among the 80 patients who met the criteria: 21 patients received bromocriptine as primary treatment (Group A); 21 patients initially received bromocriptine and then accepted microsurgery or irradiation (Group B); 38 patients had initially undergone transcranial or transsphenoidal microsurgery and then received bromocriptine or adjuvant radiotherapy (Group C). Eleven patients underwent gamma knife radiotherapy. RESULTS: In 57 patients (12 cases of Group A, 16 cases of Group B, 29 cases of Group C), the tumors on MRI had almost completely disappeared after an average follow-up period of 62 months, and in the other 23 patients, residual tumor involved the cavernous sinus. Visual symptoms improved in 33 patients while deteriorated in 7 patients. Serum prolactin level of 52 patients had in normal range after treatment (10 cases of Group A, 11 cases of Group B, 31 cases of Group C) and 7 patients were more than 9.1 nmol/L. Nine patients had symptoms of hypopituitarism. CONCLUSIONS: For IPs, individualized treatment methods are advocated in which dopamine agonist medications are effective as first-line therapy. It is necessary to take dopamine agonist after operation and close observation is mandatory. Gamma knife surgery is an option to treat the residual tumor involving the cavernous sinus.