Background: Glioblastoma, IDH-wild-type, is a highly invasive tumor, and prognosis largely depends on the extent of resection. Contrast-enhanced (CE) MRI often underestimates tumor borders, resulting in incomplete resection. Prospective multicenter evidence on positron emission tomography (PET)/magnetic resonance (MR)-guided resection planning in newly diagnosed glioblastoma remains limited. This study is the first nationwide, multicenter evaluation of 18F-fluoroethyltyrosine (FET) PET-guided glioma resection. Methods: We conducted a multicenter, prospective cohort study to evaluate the efficacy of a novel 18F-FET PET-based surgical planning system (PET/MR cross-modal tumor delineation system [PCMDS]) in glioblastoma, IDH-wild-type resection. The study comprised 239 patients: 115 underwent 18F-FET PET-guided surgery and 124 underwent CE MRI-guided surgery. The PCMDS integrated multimodal image registration and automated metabolic segmentation to delineate surgical margins. Resection outcomes were intraoperatively validated using ultrasound, MRI, and ultramicroscopic cellular imaging. Results: Compared with the CE MRI group, the 18F-FET PET group achieved a significantly higher gross total resection rate (91.3% versus 72.7%, P < 0.05) and improved survival outcomes (median overall survival: 19.7 versus 16.0 months, P = 0.0099; median progression-free survival: 12.5 versus 9.3 months, P = 0.0078). 18F-FET PET-defined margins extended beyond CE MRI-defined boundaries, and both histopathological analysis and single-cell RNA sequencing confirmed the presence of infiltrative tumor cells in 18F-FET PET-positive but MRI-negative regions. Conclusion: This multicenter study demonstrates that 18F-FET PET-based surgical planning significantly increases the extent of glioblastoma, IDH-wild-type resection and prolongs patient survival. Integrating 18F-FET PET into routine surgical practice could substantially improve clinical outcomes for patients with glioblastoma, IDH-wild-type.

BACKGROUND:Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis due to enhanced glycolytic metabolism and tumor heterogeneity. Identifying key regulators of glycolysis may provide novel therapeutic targets. METHODS:We investigated the role of DCAF13 in HCC using bioinformatics analysis, CRISPR/Cas9-mediated knockout, overexpression assays, in vitro and in vivo functional studies, and molecular dynamics simulations. m6A modification of DCAF13 was analyzed through MeRIP-qPCR and RIP assays. RESULTS:DCAF13 was significantly upregulated in HCC tissues and associated with poor prognosis. Functional assays revealed that DCAF13 promotes HCC cell proliferation, migration, invasion, and tumor growth. Mechanistically, DCAF13 directly interacts with glucose-6-phosphate dehydrogenase (G6PD), enhancing glycolytic flux. Molecular dynamics simulations confirmed the stability of the DCAF13-G6PD complex. Furthermore, METTL3-mediated m6A modification and YTHDF1 binding stabilized DCAF13 mRNA, maintaining its high expression. Silencing METTL3 or YTHDF1 reduced DCAF13 levels and impaired its oncogenic function. CONCLUSIONS:We identified a METTL3-DCAF13-YTHDF1-G6PD axis that promotes glycolytic reprogramming and HCC progression. DCAF13 may serve as a promising biomarker and therapeutic target for metabolic intervention in HCC.

Glioma, a primary intracranial malignancy with high morbidity and mortality, remains therapeutically challenging despite of advances in targeted and immune therapies. ZCCHC9, a ZCCHC family member predominantly expressed in brain cortex, has documented roles in cervical and non-small cell lung cancer, yet its function, mechanism, and clinical significance in glioma is unclear. Through multi-omics analyses leveraging TCGA, CGGA, and HPA platforms, we identified aberrant up-regulation of ZCCHC9 in glioma, particularly in grade IV, older patients, and adverse molecular subtypes, e.g., IDH wild-type, and 1p/19q non-codeletion. ZCCHC9 potentially serves as an independent biomarker for poor prognosis and diagnosis, proven by Kaplan-Meier, Cox regression, and ROC curve analyses. Reduced DNA methylation on ZCCHC9's promoter is related to a worse survival. Additionally, ZCCHC9 can remodel tumor microenvironment by promoting immune infiltration and response, influence RNA modification, and exhibit broad interactions with miRNAs, lncRNAs/circRNAs/pseudogenes. Drug-sensitivity profiling revealed its binding affinity with Temozolomide, Dabrafenib, and Trametinib. Functional validation through in vitro and in vivo experiments confirmed ZCCHC9's oncogenic role in driving proliferation and migration, while suppressing apoptosis. Collectively, ZCCHC9 induces glioma progression by immune modulation, epigenetic dys-regulation, and therapeutic resistance, positioning it as a promising diagnostic biomarker, prognostic indicator, and therapeutic target.

OBJECTIVE:Complete resection of malignant gliomas is often challenging. Our previous study indicated that intraoperative contrast-enhanced ultrasound (ICEUS) could aid in the detection of residual tumor remnants and the total removal of brain lesions. This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma.METHODS:A total of 64 patients diagnosed with malignant glioma (WHO grade HI and IV) who underwent surgery between 2012 and 2018 were included. Among them, 29 patients received ICEUS. The effects of ICEUS on overall survival (OS) and progression-free survival (PFS) of patients were evaluated. A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues.RESULTS:The ICEUS group showed better survival rates both in OS and PFS than the control group. The univariate analysis revealed that age, pathology and ICEUS were significant prognostic factors for PFS, with only age being a significant prognostic factor for OS. In multivariate analysis, age and ICEUS were significant prognostic factors for both OS and PFS. The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue.CONCLUSION:ICEUS facilitates the identification of residual tumors. Age and ICEUS are prognostic factors for malignant glioma surgery, and use of ICEUS offers a better prognosis for patients with malignant glioma.

Giant lateral ventricular meningiomas (LVMs), with the largest diameter of at least 5 cm, form a distinct subset. The incidence of giant LVMs is considered to be relatively low. Here, we evaluated clinical characteristics, and clinical outcomes after microsurgical resection, especially functional outcomes and morbidity of giant LVMs. We retrospectively reviewed 49 patients with LVMs, including 18 giant LVMs from 2012 to 2020. And we analyzed clinical, histopathological, surgical, and outcome data at our institution. Giant LVMs were most commonly present in the fourth decade of patients with the male-to-female ratio of 1:2. The most common subtypes were transitional and fibrous. Most lesions were resected via the temporal or parieto-occipital approach in our series. The median volume of blood loss was higher in the giant group (900 vs. 600 ml, p = 0.02). Meanwhile, the median length of hospital stay was prolonged for giant LVMs (20.5 vs. 16.0 days, p < 0.01). The proportion of discharged functional deterioration was higher in giant LVMs (38.9% vs. 6.5%, p = 0.02). However, there was no statistical significance between functional deterioration and tumor size at long-term follow-up (p = 0.28). Giant LVMs patients suffered from neurological and regional complications more commonly, particularly from a postoperative hematoma (4/18 vs. 1/31), and hydrocephalus (2/18 vs. 0/31). Patients with giant LVMs had a high incidence of immediate functional deterioration after microsurgery, and there was no difference in functional deterioration between the giant and non-giant LVMS during long-term follow-up. Microsurgery entails a higher complication rate in giant LVMs. We need to pay special attention to preventing postoperative hematoma and hydrocephalus.

PURPOSE:To identify risk factors for major postoperative complications in meningioma patients and to construct and validate a nomogram that identify patients at high risk of these complications. METHODS:The medical records of meningioma patients who underwent surgical resection in our hospital from January 2018 to December 2020 were collected. The patients were divided into a training set (815 cases from the main campus in 2018 and 2019) and a validation set (300 cases from two other campuses in 2020). Major postoperative complications were defined as any new neurological deficits and complications classified as Clavien-Dindo Grading (CDG) II or higher. Univariate and multivariate analyses were conducted using the training set to identify independent risk factors. A nomogram was constructed based on these results. And then validated the nomogram through bootstrap re-sampling in both the training and validation sets. The concordance index (C-index) and the area under the curve (AUC) were used to assess the discriminative ability of the nomogram. The Hosmer-Lemeshow test was performed to evaluate the goodness-of-fit. The optimal cutoff point for the nomogram was calculated using Youden's index. RESULTS:In the training set, 135 cases (16.56%) experienced major postoperative complications. The independent risk factors identified were male sex, recurrent tumors, American Society of Anesthesiologists (ASA) class III-IV, preoperative Karnofsky Performance Scale (KPS) score < 80, preoperative serum albumin < 35 g/L, tumor in the skull base or central sulcus area, subtotal tumor resection (STR), allogeneic blood transfusion, and larger tumor size. A nomogram was constructed based on these risk factors. It demonstrated good predictive performance, with a C-index of 0.919 for the training set and 0.872 for the validation set. The area under the curve (AUC) > 0.7 indicated satisfactory discriminative ability. The Hosmer-Lemeshow test showed no significant deviation from the predicted probabilities. And the cutoff for nomogram total points was about 200 (specificity 0.881 and sensitivity 0.834). CONCLUSIONS:The constructed nomogram demonstrated robust predictive performance for major postoperative complications in meningioma patients. This model can be used by surgeons as a reference in clinical decision-making.

Background and PurposeThe ability of attenuation value of the non-hypodense region of hematoma in non-contrast computed tomography (NCCT) for predicting hematoma expansion (HE) remains unclear. Our purpose is to explore this relationship.MethodsTwo cohorts of patients were collected for analysis. The region where we measured hematoma attenuation values was limited to the non-hypodense region that was not adjacent to the normal brain tissue on NCCT. The critical attenuation value was derived via receiver operating characteristic (ROC) curve analysis in the derivation cohort and its predictive ability was validated in the validation cohort. Independent relationships between predictors, such as critical attenuation value of the non-hypodense region and HE were analyzed using the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic analysis.ResultsThe results showed that the attenuation value <64 Hounsfield units (HU) was independently associated with HE [odds ratio (OR), 4.118; 95% confidential interval (CI), 1.897–9.129, p < 0.001] and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the curve (AUC) for predicting HE were 36.11%, 81.71%, 1.97, 0.78, 44.8%, 75.7%, and 0.589, respectively.ConclusionsOur research explored and validated the relationship between the attenuation value of the non-hypodense region of hematoma and HE. The attenuation value < 64 HU was an appropriate indicator of early HE.

Glioblastoma (GBM) is a type of brain cancer with high morbidity and mortality worldwide. The clinical significance, biological roles, and underlying molecular mechanisms of DNA poly ε-B subunit (POLE2) in GBM were investigated in the study. Firstly, the Cancer Genome Atlas (TCGA) database found that POLE2 was highly expressed in GBM. Immunohistochemistry (IHC) results further confirmed that POLE2 was abnormally elevated in GBM. In addition, loss-of-function assays revealed that POLE2 knockdown could inhibit the malignant behaviors of GBM, especially reduce cell viability, weaken cell clone formation, enhance the sensitivity of apoptosis, restrain migration and inhibit epithelial-mesenchymal transition (EMT) in vitro. In vivo experiments further clarified the suppressive effects of reduced POLE2 expression on tumors. Mechanically, POLE2 knockdown promoted the ubiquitination as well as reduced the stability of Forkhead transcription factor (FOXM1), which is a known tumor promotor in GBM, through Aurora kinase A (AURKA). Moreover, the knockdown of FOXM1 could weaken the promoting effects of POLE2 on malignant behaviors of GBM. In conclusion, our study revealed crucial roles and a novel mechanism of POLE2 involved in GBM through AURKA-mediated stability of FOXM1 and may provide the theoretical basis of molecular therapy for GBM.

Objective To investigate the value of routine intraoperative ultrasound (IU) and intraoperative contrast-enhanced ultrasound (ICEUS) in the surgical treatment of brain tumors, and to explore the utilization of ICEUS for the removal of the remnants surrounding the resection cavity. Methods In total, 51 patients who underwent operations from 2012 to 2018 due to different tumors in the brain were included in this study. The clinical data were evaluated retrospectively. IU was performed in all patients, among which 28 patients underwent ICEUS. The effects of IU and ICEUS on tumor resection and recurrence were evaluated. Semiquantitative analysis was performed to compare ICEUS parameters of the brain tumor with those of the surrounding tissue. Results In total, 36 male and 15 female patients were included in this study. The average age was 43 years (range: 14–68 years). The follow-up period was from 7 to 74 months (mean follow-up 32 months). IU was used in all patients, and no lesion was missed. Among them, 28 patients underwent ICEUS. The rate of total removal of the ICEUS group (23/28, 82%) was significantly higher than that of the IU group (11/23, 48%) ( P <0.05). The recurrence rate of ICEUS and IU was 18% (5/23), and 22% (5/28), respectively, and the difference did not reach statistical significance ( P >0.05). The semiquantitative analysis showed that the intensity and the transit time of microbubbles reaching the lesions were significantly different from the intensity and the transit time of microbubbles reaching the surrounding tissue ( P <0.05) and reflected indirectly the volume and the speed of blood perfusion in the lesions was higher than those in the surrounding tissue. Conclusion ICEUS is a useful tool in localizing and outlining brain lesions, especially for the resection of the hypervascular lesions in the brain. ICEUS could be more beneficial for identifying the remnants and improving the rate of total removal of these lesions than routine intraoperative ultrasound.

Recent studies have revealed that inflammation is a key factor in the causation of opioid analgesic tolerance. Opioids can induce a massive release of inflammatory cytokines and disruption of intestinal barrier function by activating Toll-like receptors 2/4 (TLR2/4), eventually resulting to sustained bacterial transmission and persistent systemic inflammation. However, most of the relevant analyses available were conducted at the level of animal experiments. It is necessary to explore the potential association between opioid tolerance and inflammatory cytokines and gut microbiota in patients with cancer pain. We retrospectively analyzed cytokines, lymphocyte subsets and blood cells in 186 cancer patients to examine the effect of oral opioids on inflammatory cytokines in patients with moderate to severe cancer pain. The control group constituted tumor patients without cancer pain, while patients with moderate to severe cancer pain taking oral opioids made up the observation group. Fecal samples collected from 25 cancer patients were also analyzed for the composition and diversity of gut microbiota using 16S rRNA sequencing to explore the association between oral opioids and dynamic changes in gut microbiota. Patients with moderate to severe cancer pain taking oxycodone had significantly higher levels of IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ than those in the control group (p < 0.001). The difference in the relative abundance of Lactobacillus (p = 0.025), Anaerostipes (p = 0.034), Megamonas (p = 0.0080), Monoglobus (p = 0.0080), and the Rikenellaceae_RC9_gut_group (p = 0.022) between the opioid and control group was significant. Oral oxycodone can cause abnormal changes in cytokine levels and gut microbiota of patients with moderate to severe cancer pain, prompting chronic systemic inflammation. Analgesic tolerance induced by long-term oxycodone use could be closely related to the consistent upregulation of IL-6 and TNF-α levels.

Objectives Glioma has a high degree of malignancy, strong invasiveness, and poor prognosis, which is always a serious threat to human health. Previous studies have reported that C2H2 zinc finger (ZNF) protein is involved in the progression of various cancers. In this study, the clinical significance, biological behavior, and molecule mechanism of ZNF655 in glioma were explored. Methods The expression of ZNF655 in glioma and its correlation with prognosis were analyzed through public datasets and immunohistochemical (IHC) staining. The shRNA-mediated ZNF655 knockdown was used to explore the effects of ZNF655 alteration on the phenotypes and tumorigenesis of human glioma cell lines. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter assays were performed to determine the potential mechanism of ZNF655 regulating Aurora kinase A (AURKA). Results ZNF655 was abundantly expressed in glioma tissue and cell lines SHG-44 and U251. Knockdown of suppressed the progression of glioma cells, which was characterized by reduced proliferation, enhanced apoptosis, cycle repression in G2, inhibition of migration, and weakened tumorigenesis. Mechanistically, transcription factor ZNF655 activated the expression of AURKA by directly binding to the promoter of AURKA. In addition, downregulation of AURKA partially reversed the promoting effects of overexpression of ZNF655 on glioma cells. Conclusions ZNF655 promoted the progression of glioma by binding to the promoter of AURKA, which may be a promising target for molecular therapy.

Abstract Background: The purpose of this study is to compare efficacy and safety of patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with frontline dasatinib 70 mg/day with those who received standard-dose dasatinib 100 mg/day. Method: From July 2019 to July 2021, 81 patients with newly diagnosed CML-CP were enrolled across 11 centers. All of the patients were randomly treated with dasatinib 70 mg/day (N=43) or standard-dose dasatinib 100 mg/day (N=38). Results: Among 81 enrolled patients, 16 patients were off study at different times for different reasons.All patients achieved hematological remission after 3 months of treatment, and the best response rates were 84.00% (21/25) and 88.89% (24/27) for 70mg/d and 100mg/d groups (P>0.05).At 6 months, the best response, complete cytogenetic response (CCyR) and major molecular response (MMR) rate were 94.44% vs 92.86% (P > 0.05), 94.44% vs 92.86% (P > 0.05) and 55.56% vs 71.43% (P > 0.05), respectively.At 9 months, the rates of CCyR and MMR were 90.91% vs 88.89% (P > 0.05) and 66.67% vs 72.73% (P > 0.05);CCyR and MMR by 12 months, respectively, were 90.91% vs 100.00% (P > 0.05), 81.82% vs 80.00% (P > 0.05).The adverse events (AEs) of the two groups were mild, and there was no significant difference (P > 0.05).The most common grade ≥3 hematological AEs in 70 mg/d group were leukopenia (1/43), neutropenia (1/43) and anemia (2/43), and In 100mg/d group were leukopenia (4/38), neutropenia (6/38), anemia (3/38) and thrombocytopenia (3/38). Conclusions: Our study suggests that patients with newly diagnosed CML-CP treated with dasatinib 70 mg/day or 100 mg/day, there is no significant difference in efficacy and safety. Decreasing the dose of dasatinib can ensure the efficacy of patients, while reducing the economic burden of patients and increasing patient compliance. Disclosures No relevant conflicts of interest to declare.

PNO1 has been reported to be involved in tumorigenesis, however, its role in glioma remains unexplored. In the present study, PNO1 expression in glioma from on-line databases, cDNA, and tissue microarrays was upregulated and associated with poor prognosis. PNO1 knockdown inhibits tumor cell growth and invasion both in vitro and in vivo; whereas PNO1 overexpression promoted cell proliferation and invasion in vitro. Notably, PNO1 interacted with THBS1 and the promotion of glioma by PNO1 overexpression could be attenuated or even reversed by simultaneously silencing THBS1. Functionally, PNO1 was involved in activation of FAK/Akt pathway. Moreover, overexpressing MYC increased PNO1 promoter activity. MYC knockdown decreased PNO1 and THBS1 expression, while inhibited cell proliferation and invasion. In conclusion, MYC-mediated upregulation of PNO1 contributes to glioma progression by activating THBS1/FAK/Akt signaling. PNO1 was reported to be a tumor promotor in the development and progression of glioma and may act as a candidate of therapeutic target in glioma treatment.

AIM:This study was designed to use in vivo and in vitro approaches to evaluate puerarin in diabetes-induced renal injury.MATERIALS AND METHODS:SD rats were divided into NC (normal control), Model (diabetic induced renal injury model), SP-L (model rats treated with low-dose standard puerarin), SP-M (model rats treated with middle-dose standard puerarin), and SP-H (model rats treated with high-dose standard puerarin) groups. We evaluated fasting blood-glucose (FBG), urinary albumin/creatinine ratio (UACR), body weight, and kidney index (KI) in the different groups. TNF-α, IL-1β, and IL-6 concentrations were measured using Elisa assays. HE staining and TUNEL assays were used to evaluate pathology and apoptosis in kidney tissues, respectively. Relative gene and protein expression was measured using RT-qPCR and Western blot assays. Apoptosis was measured using flow cytometry. The correlation between miRNA-145-5p and TLR4 was assessed using dual-luciferase reporter gene assays.RESULTS:The pathology and apoptosis cell number were deteriorate in Model group; TNF-α, IL-1β and IL-6 concentrations, FGB, UACR and KI were increased and body weight was depressed; meanwhile, relative gene and proteins expressions (miRNA-145-5p, TLR4, MyD88 and NF-κB p65) were significantly different in Model group in vivo and vitro study compared with NC group. SP treatment significantly improved the pathology and apoptosis levels in the tissues, as well as TNF-α, IL-1β and IL-6 concentrations, FGB, UACR, body weight, and KI. In vitro cell studies revealed that SP could prevent renal injury induced by diabetes through the miRNA-145-5p/TLR4 axis.CONCLUSION:SP prevents diabetes-induced renal damage via miRNA-145-5p overexpression and reduces TLR4/MyD88/NF-κB (p65) pathway activation in vitro and in vivo.

BACKGROUND:Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with a poor prognosis. DEPDC1B (DEP domain-containing protein 1B) has been shown to be associated with some types of malignancies. However, the role and underlying regulatory mechanisms of DEPDC1B in GBM remain elusive.METHODS:In this research, the expression level of DEPDC1B in GBM tissues was detected by IHC. The DEPDC1B knockdown cell line was constructed, identified by qRT-PCR and western blot and used to construct the xenotransplantation mice model and intracranial xenograft model. MTT assay, colony formation assay, flow cytometry, and Transwell assay were used to detected cell proliferation, apoptosis and migration.RESULTS:The results proved that DEPDC1B was significantly upregulated in tumor tissues, and silencing DEPDC1B could inhibit proliferation, migration and promote apoptosis of GBM cell. In addition, human apoptosis antibody array detection showed that after DEPDC1B knockdown, the expression of apoptosis-related proteins was downregulated, such as IGFBP-2, Survivin, N-cadherin, Vimentin and Snail. Finally, we indicated that knockdown of DEPDC1B significantly inhibited tumor growth in vivo.CONCLUSIONS:In summary, DEPDC1B was involved in the development and progression of GBM, which may be a potential therapeutic target and bring a breakthrough in the treatment.

Objective To explore the strategy for the surgical treatment of epilepsy patients with lesions in the central region,focusing on the effect of presurgical evaluation including intracranial recording and functional brain mapping by cortical electrical stimulation through subdural electrodes on resection of lesions,preservation of function,and control of seizure.Methods Presurgical evaluation was performed in 43 patients with epilepsy and structural lesions in the central area who underwent resection of lesion.Among them,subdural electrodes were implanted in 10 patients,followed by long-term video EEG monitoring and functional brain mapping by cortical electrical stimulation.All patients were followed up for 6-32 months.Results Presurgical EEG recorded interictal abnormalities in 28 patients (65％).Ictal discharges were captured in 16 patients,with evidence indicative of ipsilateral origin in 6 patients,and bilateral origin in 10 patients,respectively.Implantation of intracranial electrodes was performed in 7 patients without epileptiform discharges on scalp EEG,as well as in 3 patients with bilateral epileptiform discharges.Intracranial EEG recorded interictal abnormalities in 9 patients (90％) and ictal discharges in 8 patients.Functional mapping showed total overlapping of the lesion and the functional region in 2 patients,subtotal overlapping in 2 patients,and the lesion being close to the functional region in 6 patients.During follow-up,35 patients were in Engel Ⅰ (81％),7 in Engel Ⅱ (16％),and 1 in Engel Ⅲ (2％),respectively.Conclusions Resection of lesions and epileptogenic zones as well as protection of functions is of great importance in the surgical treatment of epilepsy patients with lesions in the central region.Intracranial EEG recording and functional brain mapping by electrical cortical stimulation contribute to further localization of epileptogenic focus and identification of the relation and overlapping of the lesion,epileptogenic focus and the functional region.

The purpose of this study was to evaluate the effect of adenosine A2A receptor antagonist ZM241385 on amygdala-kindled seizures and its roles in epileptogenesis. Electrodes were implanted into the right amygdala of male adult Wistar rats. Kindling was accomplished by using stimulus strength of 500 μA applied daily to the amygdala until 10 consecutive stage 5 seizues were induced. Then effect of ZM241385 was studied in fully kindled rats after intracerebroventricular administration of the drug. In addition, the effect on kindling progression was evaluated through ZM241385 injection before daily stimulation. In all experiments, behavioral changes in the rats in response to ZM241385 were monitored closely. The results showed that, in fully amygdala-kindled rats, ZM241385 (0.001–0.1 nmol/L) decreased afterdischage duration (ADD), motor seizure duration (MSD), stage 5 duration (S5D) and seizure duration (SD), but only the effect on ADD was dose-dependent. The doses of 0.001–0.1 nmol/L had no influence on stage 4 latency (S4L) and seizure stage (SS). The dosages of 0.0001 and 1 nmol/L of ZM241385 did not exert any effect on all seizure parameters. In contrast to the results in fully amygdala-kindled rats, ZM241385 (0.001–0.1 nmol/L) had minimal or no effects on the progression of amygdala-kindled seizures. We are led to the conclusion that although ZM241385 had no influence on the progression of amygdala-kindled seizures, it had potent anti-convulsant profile and little adverse effects at the dosage of 0.001–0.1 nmol/L, suggesting that the agent is effective against the amygdala-kindled seizures.

Cytokine-induced killer (CIK) cells are immune effector cells characterized by co-expression of CD3 and CD56 molecules. We examined the quantities of CIK cells and the changes of these cell expressing NK cell receptors in HIV-1-positive children infected via mother-to-child transmission. The percentage of CIK cells was quantified and the changes in the surface cell receptor profiles in 18 HIV-1-infected children were examined. We found that CIK cell percentages were dramatically increased in HIV-1-infected children. Furthermore, the expressions of CD16, NKp30, NKp44, NKp46, NKp80 and CD244 on CIK cells were decreased, while the expressions of KIR3DL1 and NKG2D on CIK cells were increased in HIV-1-infected children. However, the expressions of KIR2D and NTB-A on CIK cells did not change in the HIV-1-infected children. CIK cells possessed the characteristics of promoting the maturation of dendritic cells and killing functions in HIV-1-infected children. Moreover, serum concentrations of IL-4 and IFN-γ were significantly increased in HIV-1-infected children compared with the HIV-negative controls. These changes likely occurred as a protective mechanism against transmission of maternal HIV-1 virus and thereby helped to limit viral spread, eliminate infected cells and help HIV-1-infected patients to slow the progression to AIDS.

Objective To investigate the change of phosphorylation of JNK in the hippocampus of epilepsy rats kindled by chronic electrical stimulation in the basolateral nucleus of the amygdala. Method Eighty male Wistar rats were randomly divided into 3 groups:15 in blank control group,15 in sharn group and 50 in kindling group.The amygdala of the rats in the kindling group was stimulated with constant pulse current. Rats'seizures and electroencephalogram were recorded throughout the stimulation process.JNK phosphorylation level in the rat hippocampus was detected by Western blot. TUNEL staining and immunohistochemical staining of GFAP were performed to evaluate the neuronal death and gliosis in the hippocampus. Results Thirty-six rats were kindled successfully 12 to 20 days after the kindling began.The level of JNK phosphorylafion in the hippocmnpns was significantly higher in kindled rats(2.39±0.14)than those in other two groups(1.13±0.06 in the sham group,1.11±0.77in control group)(P<0.05).There was no significant difference in JNK phosphorylation between the sham group and the control group(P>0.05).Expression of GFAP in the hippocampus of kindled rats was significantly stronger than those in the blank control group and in the sham group(P<0.05).TUNEL staining positive cells in the hippocampus of kindled rats were significantly more than those in the blank control group and in the sham group(P<0.05).Conclusions The level of JNK phosphorylation in the hippocampns increases in the amygdala kindled rats.JNK signal transductiou pathway may be involved in the process of hippocampal sclerosis in the mesial temporal lobe epilepsy.