Objective To study the diversities of imaging, symptoms, electrophysiology and clinical value of the stereoelectroencephalography(SEEG) in patients with mesial temporal lobe epilepsy.Methods Eight patients with intractable epilepsy in Epilepsy Center of Yuquan Hospital of Tsinghua University who underwent mesial temporal lobectomy were recruited in this study, and their epileptic foci could not be accurately positioned.Therefore stereotactic brain electrodes were implanted, and their usual attack originated from mesial temporal lobe structure were confirmed.There was no seizure in the one year follow-up.Results Symptoms of the eight patients behaved differently, and the onset of the seizures in scalp electroencephalograph or SEEG showed diversities.Epileptic discharges were found originated from the mesial temporal lobe after implanting electrodes: in the early stage of discharges, four cases had the conduction to insular lobe structure;two cases had the conduction to contralateral mesial temporal lobe;one case had the conduction to retrosplenial cortex;one case had the conduction to parietal lobe;one case had the conduction to frontal lobe and rapid generalization (one case had the conduction to insular lobe and contralateral mesial temporal lobe meanwhile).Conclusions There is difference in clinic, imaging and electrophysiology of the patients with mesial temporal lobe epilepsy The non-specificity can be explained by the evolution of the intracranial electroencephalography, which can help us know its network conduction pattern Insular lobe is the most common conduction approach of mesial temporal lobe epilepsy in early stage SEEG can be used as a microinvasive, accurate preoperative localization method, which can help us to locate accurately and understand the discharges and conduction mode.

Background Various studies demonstrated that the apoptosis of lens epithelial cells(LECs) is associated with the overexpression of the c-myc gene in LECs induced by galactose.Inhibiting the abnormal expression of the c-myc gene in LECs is an effective approach to mitigate the pathogenesis and development of cataract.Objective The goal of this study is to investigate the inhibitory effects of c-myc antisense oligodeoxynucleotide(c-myc ASODN) on the apoptosis of LECs in the eye with galactose-induced cataract.Methods Galactose-induced cataract models were established by the retrobulbar injection of 0.2 mL of 20% galactose once per day.Lipo-antisense oligodeoxynucleotide(Lipo-ASODN,0.2 mL) was retrobulbarly injected 4 hours after the injection of galactose at one-day intervals.The animals were sacrificed and lenses were obtained to evaluate the apoptosis of LECs and the effect of c-myc ASODN on LECs apoptosis induced by galactose was examined by TUNEL assay after 7,14 and 24 days.The ultrastructural changes of LECs were examined under the transmission electron microscopy(TEM).Results A significant difference in the apoptotic rate of LECs was found among the 7 day,14 day and 24 day groups(F_(7 days)=3 418.495,P＜0.01;F_(14 days)=1137.555,P＜0.01;F_(24 days)=2198.871,P＜0.01).The apoptotic rate of LECs in the galactose group was markedly higher than that in the normal saline solution group 7 days,14 days and 24 days after the experiment(P＜0.01).The apoptotic rate of LECs in the galactose+lipo+ ASODN group significantly declined in comparison to the galactose group after 7 days,14 days and 24 days(P＜0.05).TUNEL assay showed the condensation,breakage and irregularity of the nuclei of apoptotic cells in the galactose group.The destruction of the ultrastructure of the cells and organelles were observed under the transmission electron microscope.Conclusion Galactose induces apoptosis of LECs in cataractogenesis.C-myc ASODN inhibits apoptosis of LECs induced by galactose.

Objective To propose a novel stereo-electroencephalography(SEEG) quantitative measure analyzing ictal high frequency (60-90 Hz) and calculating high frequency epileptogenicity index (HFEI) to localize epileptogenic zone and evaluate epileptogenic network. Methods The clinical presurgical evaluation and SEEG data of 15 patients who were performed SEEG electrodes implantation from April 2015 to March 2016 were analyzed retrospectively. Post-implantation head CT images and 3D MRI data were fused for accurately identifying and locating each electrode contact. Ictal SEEG quantitative measure HFEI was calculated and threshold was set. The epileptogenic network was divided into focal, regional, multiple regional and bilateral ones and the results were compared with the pathological results.Results The epileptogenic network was focal for four patients, regional for four patients, multiple regional for six patients and bilateral for one patient (7/15). In terms of the pathology,two cases with hippocampal sclerosis both showed regional network. In four cases with cerebral malacia, two cases showed multiple regional network and the other two cases showed focal network. In six cases with cortical malformation, three cases showed multiple regional network, the other three cases showed focal, regional and bilateral networks respectively. Conclusions We explored a novel SEEG quantitative measure based on the high frequency power analysis,which is objective and could localize epileptogenic zone and evaluate the epileptic network.

Objective:To analyze the characteristics of stereoelectroencephalography (SEEG) in children with drug-resistant epileptic spasms (ES), and to explore the surgical strategy of children with spastic seizure under the guidance of SEEG.Methods:The clinical data of 156 children with ES who were preoperatively evaluated in the Department of Neurosurgery Ward 3, Tsinghua University Yuquan Hospital from January 2014 to December 2021 were retrospectively reviewed.All children were evaluated in the second stage of stereotactic electrode placement after a non-invasive preoperative evaluation.The characteristics of intracranial EEG, surgical strategy and prognosis were analyzed.Results:A total of 19 eligible children were included, involving 13 boys and 6 girls.The age of first onset and surgical age of them ranged 1 month to 4 years, and 2 years to 13 years, respectively.The SEEG was divided into 3 types in children with ES at the onset.Five children were SEEG type A, presenting with the focal seizure discharges at the beginning and a gradual propagation to widespread fast-wave bursts.Ten children were SEEG type B, presenting a focal leading spike followed by diffused fast-wave bursts.Four children were SEEG type C, presenting a diffuse fast wave rhythm onset.Although some electrode discharges appeared slightly " leading", they covered more than one brain region.After focal resection or thermocoagulation, 13/19 patients did not have the onset of seizures, and 5/19 and 8/19 were graded as SEEG type A, and B, respectively.During the intermittent period of SEEG attacks in children with SEEG type A and B, a significant phenomenon of focal epileptic discharge consistent with the onset of the attack was observed, and surgical removal of these areas effectively controlled spastic seizures.Conclusions:Epileptic spasms may be triggered by a focal neocortical discharge.Intracranial EEG showed that the focal seizure onset evolves into spasm or a focal " leading spike" is a good indicator of surgical prognosis.

Objective To test the immune therapeutic effects of PICKCa adjuvant rabies vaccine for the post-exposure mice and beagle dogs and immune memory effect for human.Methods For the mice and beagle dogs first to infect with rabies wild virus and then immunize with PICKCa rabies vaccine.For volunteers, first to immunize with PICKCa rabies vaccine after 2.5 years to take peripheral blood mononuclear cell and then to check cells secreted interferon-gwith flow cytometry. Results In 3 independent assays of post-explosure immunization of mice and beagle dogs PICKCa rabies vaccine were much better then commercial adjuvant-free rabies vaccines, the protective rate from 20%-30%to 70%-100%Also, in the assay of cells secreted IFN-γby peripheral blood mononuclear cells from volunteers immunized by PICKCa rabies vaccine the IFN-γcell levels were much higher than control.Conclusions Compared with commercial adjuvant-free rabies vaccines the PICKCa rabies vaccine had significant immune therapeutic effects in the mice and dogs.Also PICKCa rabies vaccine had good immune memory effect in human.

Proteolysis targeting chimeria (PROTAC) degrades target proteins by utilizing the ubiquitin-proteasome pathway, subverting the concept of traditional small molecule inhibitors. Among the common mutation targets of non-small cell lung cancer (NSCLC), PROTAC technology has successfully achieved the effective degradation of kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK ) and other proteins in preclinical studies. PROTAC drugs with their unique event-driven advantages, are expected to overcome acquired drug resistance caused by small molecule inhibitors and show good therapeutic potential for undruggable targets, thereby providing a new strategy for the treatment of NSCLC.
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Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proteolysis ; Proto-Oncogene Proteins p21(ras)/genetics*

Objective:To investigate the safety and efficacy of FOLFOX (5-fluorouracil + calcium folinate + oxaliplatin) hepatic arterial infusion chemotherapy (FOLFOX-HAIC) combined with immune and targeted therapy as triple combination therapy for patients with single China Liver Cancer Staging (CNLC) Ⅰb hepatocellular carcinoma.Methods:A total of 20 patients with single CNLC Ⅰb hepatocellular carcinoma who received FOLFOX-HAIC combined with immune and targeted therapy as triple combination therapy in the First Affiliated Hospital of Guangxi Medical University from October 2021 to August 2022 were included. The clinical data of all patients was retrospectively analyzed. There were 18 males and 2 females, with the age of (55.1±9.9) years. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were used to evaluate the efficacy of FOLFOX-HAIC combined with immune and targeted therapy, and the clinical safety of triple combination therapy was evaluated by common terminology criteria for adverse events 4.0.Results:According to RECIST 1.1, objective response rate of 20 patients was 70.0% (14/20) and disease control rate was 100.0% (20/20) after 2 cycles of treatment (one cycle of FOLFOX-HAIC plus programmed death-1 antibody). According to mRECIST, objective response rate was 90.0% (18/20) and the disease control rate was 100.0% (20/20) after 2 cycles of treatment. Following the treatment, 12 patients (60.0%) received liver tumor resection, and all of them achieved R 0 resection, 2 patients (10.0%) received radiotherapy, 3 patients (15.0%) stopped drug treatment for surgery, 2 patients (10.0%) refused surgery, and 1 patient (5.0%) died of multiple organ failure caused by immune hepatitis. According to pathological results, 3 patients (25.0%, 3/12) achieved pathological complete response, and 4 patients (33.3%, 4/12) achieved major pathological response. In the safety evaluation, the overall incidence of adverse events was 100.0% (20/20). Seven patients (35.0%) had grade 3 adverse events and 1 patient (5.0%) died of multiple organ failure due to immune hepatitis (grade 5). Grade 1-3 adverse events could be relieved after symptomatic treatment. Conclusion:The triple combination therapy of FOLFOX-HAIC combined with immune and targeted therapy is safe and has high objective response rate and disease control rate, which could be a new strategy for the neoadjuvant treatment of hepatocellular carcinoma.

Objective:To study the localization value of stereoelectroencephalography (SEEG) in refractory epilepsy associated with tuberous sclerosis complex (TSC), and to analyze the prognosis related factors.Methods:A case control study.Data of 66 patients with TSC-related refractory epilepsy who underwent SEEG placement at the Epilepsy Center of Tsinghua University Yu-Quan Hospital from January 2014 to March 2023 were retrospectively analyzed, including medical history, seizure semiology, scalp electroencephalogram (EEG), imaging, and SEEG findings.Patients were divided into a seizure-free group and a seizure group according to the seizures after surgery. t/ χ2 test was used to compare the relationship between age of onset, age of surgery, duration of epilepsy, genetic findings, seizure symptoms, scalp EEG characteristics, SEEG placement protocol and prognosis. Results:A total of 66 patients met the enrollment criteria, of whom 55 patients were seizure-free after surgery (seizure-free group), and 11 patients still had seizures (seizure group).Among the 66 patients, there were 46 males and 20 females; the age of onset was (21.72±30.01) months; the age of SEEG surgery was (6.79±5.12) years; the duration of epilepsy was (4.98±4.11) years.SEEG results showed that seizures started with a single tuber in 43 patients (64.4%), seizures started with 2 or more tubers in one hemisphere in 16 patients, and 7 patients had bilateral multi-tubers or the pathogenic tuber(s) could not be identified.The following factors were found to be associated with prognosis: early age of surgery ( t=-3.463, P<0.01), ictal scalp EEG with a definite lateralization ( χ2=7.876, P<0.05), and the concordance of interictal and ictal EEG ( χ2=6.821, P<0.05).The age of onset, duration of epilepsy, seizure type and symptom, genetic findings, and SEEG placement protocol were not significantly correlated with prognosis.The results of SEEG identified that onset with a single tuber revealed a better postoperative outcome. Conclusions:This study confirms the safety and efficacy of SEEG in TSC-related refractory epilepsy, and also finds that ictal EEG is uniquely valuable in guiding SEEG placement for TSC-related refractory epilepsy, which can help us better select patients with TSC-related refractory epilepsy who are suitable for SEEG placement.