[ Abstract] Ischemic brain injury is closely associated w ith oxidative stress, neuron loss, and inflammatory reaction. The thioredoxin system is an important antioxidant system in human body. It plays the important roles in the process of fighting against oxidative stress damage, inhibiting apoptosis and inflammation. In recent years, the roles of thioredoxin system in cerebral ischemia have attracted more and more attention. This article review s the roles of thioredoxin in cerebral ischemia.

Objective To observe the effects of acupuncture on oxidative stress and neuronal damage in the prefrontal cortex of chronic cerebral hypoperfusion (CCH) rats; To investigate the molecular mechanisms of acupuncture in cognitive impairment of vascular dementia (VD) rats. Methods The animal model of VD was replicated by permanent bilateral common carotid artery occlusion (2VO) to induce CCH in rats. After modeling, rats were randomized into model group, acupuncture group and non-acupoint group. Sham-operation group was set as control group. Rats of acupuncture group and non-acupoint group were treated with needling for 2 weeks at 3 days after 2VO. Nissl and DHE staining were respectively used to evaluate the numbers of neurons and ROS level. SOD activity was examined by xanthine oxidase technique. Results Compared with sham-operation group, the number of neurons and SOD activity decreased in the model group, while the ROS level increased. Compared with the model group, the number of neurons and SOD activity increased in the acupuncture group, while the ROS level decreased. There were no obvious changes in all indexes in non-acupoint group. Conclusion Acupuncture can inhibit oxidative stress and improve neuronal damage and loss in the prefrontal cortex of VD rats.

Objective To observe the effects of acupuncture on synaptic transmission signal molecules in rats with vascular dementia (VD), such as PKC, CaMKⅡ and NR2B, and discuss the molecular mechanism of acupuncture treatment for VD.Methods The multi-infarct dementia model was established by injection of emboli into the internal carotid artery. Experimental rats were randomly divided into normal group, model group, acupuncture group and non-acupoint group. For acupuncture group, acupuncture needles were penetrated into bilateral Zusanli. Non-acupoint group was given acupuncture treatment at the bilateral hypochondrium (10 mm above iliac crest). The rats in normal group and model group were performed to the same amount of capture stimulation as the acupuncture and non-acupoint groups. After treatment, the hippocampal PKC activity was detected by ELISA. Western blot was used to detect CaMKⅡ expression, and the protein expression of NR2B in CA1, CA3 and DG zones was assayed by immunohistochemical staining.Results Compared with normal group, PKC activity and NR2B expression in the hippocampus significantly decreased in the model group (P<0.01). After the acupuncture treatment, PKC activity increased significantly (P<0.05), and the protein expression of NR2B showed a trend to increase. There was no obvious difference in CaMKⅡ expression among all groups.Conclusion Acupuncture at Zusanli can enhance the activity of hippocampal PKC, a synaptic transmission signal molecule, which maybe one of the important molecular targets for the treatment of VD.

Objective To investigate the treatment value of intensified chemotherapy combined with intrathe-cal Methotrexate(ITMTX)in the treatment of children with relapsed medulloblastoma.Methods From February 2011 to February 2014,40 relapsed patients in Beijing Shijitan Hospital,Capital Medical University,aged 10.6 years(2.7 to 17.7 years),were received 4 cycles of carboplatin and Etoposide continuously infusion for 96 h,and sequentially fo-llowed with Ifosfamide,Etoposide and Nedaplatin for 3 cycles,then administrated oral Temozolomide(TMZ)and Etopo-side for 12 cycles.All patients were divided into ITMTX group,which were performed ITMTX during every chemothera-py or every 3 weeks,and no intrathecal Methotrexate(no-ITMTX)group,which were not performed with ITMTX.Re-sponses were evaluated,and the objective response time,time to tumor progress(TTP),time to treatment failure (TTF),and recurrence-free interval(RFI)of the two groups were contrasted.The side-effects of chemotherapy and ITMTX were analyzed,overall survival was calculated using Kaplan-Meier method,and chi-square test or t test was used to compare the difference between two groups.Results Until 30thDecember 2016,the follow-up time was 29.4 months(ranging from 2 to 57 months). The 3-year overall survival(OS)rate was(53.5 ± 8.1)%,and 45.0% pa-tients were objective response,and the mean objective response time was 2 months,and the RFI was 18 months.For IT-MTX patients,the 3-year OS rate was(66.6 ± 11.5)%,the objective response ratio was 70.0%,and mean objective response time was 1.5 months,24 months free-event of TTP and TTF was 70.0% and 90.0%,respectively,and the RFI was 22.5 months.For no-ITMTX patients,the 3-year OS rate was(40.0 ± 11.0)%,objective response ratio was 20.0%,and mean objective response time was 2.5 months(1.5-4.0 months),24 months free-event of TTP and TTF was 35.0% and 50.0%,respectively,and the RFI was 5 months(0-40 months).Compared with those of no-ITMTX patients,the RFI,24 months TTP and TTF of ITMTX patients were much better,there were statistical signi-ficances(all P<0.05).The main side-effects of chemotherapy was gastrointestinal hematologic side-effects,and re-covered quickly with supportive treatment.No obvious Methotrexate induced neurotoxicity was found.Conclusion Based on high-dose chemotherapy,ITMTX can further improve the long-term survival of patients with relapsed medulloblas-toma,and it is more feasible and suitable for relapsed MB children in China.

Objective To analyze the survival rate and adverse effect of therapy of childhood supratentorial primitive neuroectoderma (sPNET)patients in order to investigate a suitable therapy. Methods Between December 2012 and December 2014,18 children,aged from 0. 6 to 13. 6 years old,were treated with pediatric himtumor(HIT)-2000 protocol in Beijing Shijitan Hospital,Capital Medical University. All patients were performed tumor gross total re-section,and someone accepted irradiation therapy firstly. The adverse effect of radiotherapy and chemotherapy was ana-lyzed,and the 3 - year progression - free survival (PFS)rate and overall survival (OS)rate were calculated by using Kaplan - Meier method. Results Till September 2017,the mean follow - up time was 3. 0 years (0. 2 - 4. 8 years), and the survival rate was 72. 2％ (13 / 18 cases). Eleven cases(11 / 18 cases,61. 1％)were complete remission,but 7 cases (7 / 18 cases,38. 9％)relapsed during or after therapy. The 3 - year PFS and OS rates were (66. 7 ± 11. 1)％and (71. 8 ± 10. 7)％,respectively. Moreover,14 patients received craniospinal irradiation,and their 3 - year PFS and OS rates were (68. 8 ± 13. 3)％ and (85. 7 ± 9. 4)％,respectively,there was no significant difference between the overall rates(all P >0. 05). During the follow - up period,all patients were not involved radiation - reduced brain necro-sis,myelitis,and pancreatic injury. During the whole central radiotherapy,14 children had different degree of blood rou-tine abnormalities,mainly manifested in leukocytes and thrombocytopenia,and the blood routine was restored to normal after subcutaneous injection of granulocyte stimulating factor. The adverse reactions of the gastrointestinal tract were re-latively mild,mainly nausea and vomiting,and the improvement of the gastric mucosa and the protection of the gastric mucosa were all improved. The gastrointestinal tract adverse reactions caused by HIT - 2000 were mainly nausea,vomi-ting,abdominal pain,diarrhea,constipation,and so on. The incidence of hematological adverse reactions was high,up to 100％,of which 2 cases were cured by active anti infection and symptomatic treatment due to the lack of granulocytic and fever. Conclusion HIT - 2000 protocol is a feasible and efficient therapy method for sPNET of Chinese children patients,and the adverse effects are tolerable.

Objective To investigate the early diagnosis and treatment of craniospinal irradiation(CSI)in-duced lung injury (RILI)in children with malignant brain tumors.Methods From January 2014 to January 2016,a total of 145 children with malignant brain tumors from Beijing Shijitan Hospital,Capital Medical University were enrolled in this study.All children received postoperative CSI.Ten children were diagnosed as RILI by high－resolution computed tomography (HRCT)scanning before the start of subsequent chemotherapy and 42 days after CSI.Oral Pred-nisone acetate tablets 0.5－1.0 mg/(kg·d)were given to treat RILI and compound Sulfamethoxazole to prevent sec-ondary lung inflammation.Antibiotic treatment and symptomatic support were given to 2 patients because of the com-bined infection.Then every 4 weeks HRCT was performed and the dosage of Prednisone was adjusted.Clinical charac-teristics and treatment effects were observed synthetically.Results Up to January 2018,the median follow－up time was 28 months (ranged from 26 to 48 months),only 10 patients suffered from RILI,and the morbidity was 6.9%.Eight of 10 patients had medulloblastoma,1 case with pineoblastoma,and 1 case with atypical teratoma/rhabdomyoid tumor. They were 6 boys and 4 girls,and the median age was 8 years old (ranged from 5 to 13 years old).The time points of diagnosis of lung damage were 39－52 days after the end of radiotherapy,and lesions were located in the dorsal or basal segments of lower lobe of unilateral or bilateral lung in HRCT scanning.No obvious respiratory symptoms or other dis-comfort was found except for frequent cough in 2 patients.Lung lesions were gradually reduced and disappeared within 2 to 8 months after treatment with Prednisone and compound Sulfamethoxazole.Two cases suffered severe infection be-fore or during the subsequent chemotherapy,and the condition was gradually improved after anti－infection treatment based on drug sensitivity test.Then subsequent chemotherapy underwent successfully.Conclusions RILI presents mild symptoms or asymptomatic.Routine lung imaging after radiotherapy is beneficial to the early diagnosis of lung damage, and early treatment with Prednisone and prophylaxis with compound Sulfamethoxazole has a good prognosis.

Objective:To analyze the clinical characteristics of children with medulloblastoma (MB) complicated with incomplete intestinal obstruction, and to explore the possible pathogenesis of intestinal obstruction in children with MB.Methods:A total of 409 children with MB admitted to the Department of Pediatrics of Beijing Shijitan Hospital, Capital Medical University from October 2014 to January 2019 were recruited into this study, and the clinical data of children with incomplete intestinal obstruction were collected and analyzed retrospectively.A comparison was performed between these children and those without intestinal obstruction who were treated at the same time.The chi- squared test and Logistic regression analysis were adopted to explore the pathogenesis of intestinal obstruction.The overall survival (OS) rate was calculated with the Kaplan-Meier method. Results:There were 11 cases of 409 children with MB complicated with incomplete intestinal obstruction in total, with the morbidity of 2.7%, they were all over 3 years old, with the median age of 8.7 years, and a male-to-female ratio of 4.5∶1.The incomplete intestinal obstruction in all cases occurred during the first cycle of maintenance chemotherapy after radiotherapy.All these patients could be reco-vered after conservative treatment, and no incomplete intestinal obstruction occurred in the subsequent chemotherapy.The results of Logistic regression analysis showed that there was a correlation between age and the development of incomplete intestinal obstruction ( P<0.05). The 2-year OS rate of MB patients complicated with incomplete intestinal obstruction was (87.5±11.7)%, and that of patients without incomplete intestinal obstruction during the same period was (92.8±1.6)%, which showed that the difference between the two group was not statistically significant ( P>0.05). Conclusions:Incomplete intestinal obstruction would occur in all MB patients within 2 months after radiotherapy, and children more than 3 years old are more prone to suffer from this disease.Therefore, it can be supposed that gastrointestinal mucosa was damaged under the double attack of radiotherapy and Vincristine, which slowed down the intestinal peristalsis, thus inducing intestinal obstruction.

Objective: To investigate the prognostic factors and survival status of children with medulloblastoma (MB) by using retrospective analysis. Methods: From February 2011 to December 2017, 224 children with newly-diagnosed MB were enrolled in this study, which was carried out at Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University.The overall survival (OS) rate and progression-free survival (PFS) rate were calcula-ted by using Kaplan-Meier method, the difference between 2 groups was tested by Log-rank method, and prognostic factors were analyzed by COX regression. Results: Until December 30, 2018, the median survival time of all these 224 children was 4.1 years, the survival rate was 74.6%, complete response (CR) rate was 60.3%, and the relapse rate was 1.7%. The 5-year PFS rate and 5- year OS rate of all patients were (58.2±3.6)% and (72.5±3.3)%, respectively. Survival rates of children in the high-risk group, with metastatic disease, aged <3 years, and with positive tumor cells in the cerebrospinal fluid(CSF) were very low. The 5-year OS rates were (54.8±5.3)%, (57.7±5.9)%, (41.6±8.7)%, and (53.0±7.3)%, respectively.Compared to others, the children with MB large-cell/anaplastic histology [5-year OS rate was (35.3±13.6)%] and MB group 3 subtype [3-year OS rate was (25.0±13.0)%] lived a miserable life.Meanwhile, the children in the stand-risk group, without metastatic disease, no large-cell/anaplastic histology, age older than 3 years, and with tumor cell negative in CSF, lived a better life. The 5-year OS rates were (87.5±3.5)%, (80.3±3.7)%, (70.6±5.5)%, (78.3±3.3)%, and (78.4±3.5)%, respectively, and all of them were over 70.0%. No WNT tumors progressed or relapsed, and 5- year OS rate was 100.0%. The survival status of SHH subgroup was inferior to that of group 4 subtype[(64.8±5.8)% vs.(83.5±3.8)%, χ²=5.417, P=0.015]. With COX analysis, age and tumor cells in CSF at the time of diagnosis were independent risk factors for OS and PFS of MB (PFS: Wald=8.485, P=0.004; Wald=11.702, P=0.001; OS: Wald=16.274, P=0.000; Wald=7.191, P=0.007). Conclusions Survival of children with MB more than 3 years old has been reached a perfectly high level.Age and tumor cells in CSF are independent risk factors for the OS and PFS. However, the prognosis of large-cell/anaplastic histology, malignancy cell positive in CSF, group 3 and children under 3 years old, is still poor, and intensive treatment is needed urgently for those patients.

Objective:Summarizing the clinical characteristics of extraneural metastasis in childhood medulloblastoma.Methods:A total of 616 cases with medulloblastoma treated in Beijing Shijitan Hospital from April 2010 to April 2019 were analyzed retrospectively, among which 11 cases developed extraneural metastasis.The age of onset, location and time of extraneural metastasis, pathological and molecular typing, treatment and prognosis were descriptively analyzed.The differences of blood biochemical indexes between medulloblastoma cases with and without extraneural metastasis were statistically analyzed by t test. Results:As of February 2020, the median follow-up period was 16 months (ranging from 3 to 69 months). Eleven cases, including 8 males and 3 females, were diagnosed with extraneural metastasis, with the incidence being about 1.8%.The median age of medulloblastoma was 6 years (2-10 years), and the median age at presentation of extraneural metastasis was 7 years (2-12 years). Extraneural metastasis occurred from 0.5 months to 38.0 months after the operation, and the affected location includes bone (6 cases), bone marrow (3 cases), lung (3 cases), pelvis (2 cases) and abdominal cavity (1 case). In these patients, the range of lactic dehydrogenase (LDH) was (2 298.00±1 570.70) U/L and neuron-specific enolase (NSE) was (201.00±68.34) μg/L, which were significantly higher than those in patients without extraneural metastasis [(249.50±46.28) U/L and (22.80±7.12) μg/L, all P<0.05]. Partial patients were treated with chemotherapy, while the majority of them were treated with palliative treatment in the terminal stage, with the survival period mostly less than 10 months. Conclusions:Although there is a low incidence of extraneural metastasis in medulloblastoma pediatric patients, the prognosis of these patients with extraneural metastasis is poor and most of them would die within one year.The most common sites include bone, followed by bone marrow and lungs, which may be related to the spread of cerebrospinal fluid and the increased levels of LDH and NSE.

Objective:To explore the effect of neutrophil-lymphocyte ratio (NLR) at the initial visit on the survival of children with newly diagnosed medulloblastoma (MB).Methods:This was a case-control study involving 61 children with newly diagnosed MB at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University from August 2018 to January 2020 .The blood cell counts, lymphocyte subsets and immunoglobulin in the periphe-ral blood were measured to calculate NLR at the initial visit.Based on the cut-off value determined by receiver opera-ting characteristic (ROC) curve, patients were divided into high NLR group (≥ 2.07, n=21) and low NLR group (<2.07, n=40). The progression-free survival (PFS) and overall survival (OS) between 2 groups were analyzed by the Kaplan-Meier method, followed by Log- rank test.The correlation between NLR at the initial visit with clinical characteristics, lymphocyte subsets and immunoglobulin of children with newly diagnosed MB was analyzed.Differences between groups were compared by the Chi- square test, Mann- Whitney U test and independent sample t test. Results:The survival analysis showed that the relapse rate (38.1% vs.10.0%, χ2=6.879, P=0.016) and mortality rate (19.0% vs.0, χ2=8.154, P=0.011) were significantly higher in high NLR group than those of low NLR group.PFS (12 months vs.19 months, χ2=9.775, P=0.002) and OS (19 months vs.20 months, χ2=8.432, P=0.004) were significantly shorter in high NLR group than those of low NLR group.No significant differences in clinical characteristics were detected between groups (all P>0.05). Compared with low NLR group, the percentage of T lymphocyte[(67.93±6.37)% vs.(73.38±8.08)%, t=2.886, df=48.865, P=0.006], T helper cells (Th)[(30.86±5.53)% vs.(34.29±7.44)%, t=2.037, df=51.981, P=0.047], and T suppressor cells (Ts)[(27.39±5.50)% vs.(30.84±6.58)%, t=2.164, df=47.581, P=0.035] were significantly lower in high NLR group.Spearman correlation analysis showed a negative correlation between NLR and T lymphocyte count ( r=-0.303, P=0.018), and Ts lymphocyte count ( r=-0.260, P=0.043). Conclusions:Children with newly diagnosed MB expressing a high level of NLR had a poor prognosis, which may be associated with T lymphocyte and Ts lymphocyte.