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 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 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 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.

Cerebral infarction, with high incidence, high mortality, high disability and high recurrence rates, can impose a serious burden on families and society. After cerebral infarction occurrence, neurons, as the fundamental structures of the central nervous system, are unable to renew or multiply after death; hence, full recovery from neurological impairments following cerebral infarction is challenging. With stem cell and genetic recombination advancements, cellular replacement therapy after cerebral infarction progresses, which helps clinical transformation and application. In this paper, the basic researches of cellular replacement therapy after cerebral infarction are reviewed from 3 aspects: endogenous nerve regeneration, exogenous stem cell transplantation, and in situ somatic cell trans-differentiation into neurons, in order to provide references for cerebral infarction treatment

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.

OBJECTIVE To detect and evaluate the signals of amlodipine and lercanidipine -induced adverse drug events （ADE）. METHODS All ADE reports about “amlodipine”and“lercanidipine”were searched from FAERS database during Jan . 1st，2004 to Sept . 30th，2021. Reported odds ratio and Bayesian confidence propagation neural network were used to detect ADE signals. The moderately strong signals and strong signals in key systems were selected for analysis . RESULTS From FAERS database，249 657 and 10 558 reports were extracted with amlodipine and lercanidipine as suspect drugs ，respectively. In this study，62 and 58 signals related to amlodipine and lercanidipine were detected respectively . At the same time ，moderately strong signals of peripheral edema ， hypotension， orthostatic hypotension and hypovolemic shock were detected in the twodrugs，all of which were common adverse reactions of the two drugs. The special ADEs detected in this study were as follows： in the respiratory system ， chest and mediastinaldisease system ，strong signals of non -cardiogenic pulmonary edema were detected for amlodipine ，and strong signals of dyspnea at rest for lercanidipine ；in gastrointestinal diseases ，strong signals of gingival hypertrophy were detected only for amlodipine；in skin and subcutaneous tissue disease system ，moderately strong signals related to “vasculitis”were detected for both drugs，moderately strong signals related to linear IgA disease were detected for amlodipine ，and moderately strong signals related to bullous dermatitis were detected for lercanidipine ；in the renal and urinary system disease system ，the signals of acute renal injury were detected for both drugs （amlodipine was detected as a moderately strong signal ，and lecardipine was detected as a strong signal ）； in the mental system ，moderately strong signals related to suicide were detected for amlodipine . Both hypotension and acute renal injury ranked in the top two in the number of reports of the two drugs . The time scan results of the information component （IC）of this study showed that the IC values of non -cardiogenic pulmonary edema and suicide completion signals of amlodipine increased from 0.76，－0.49 to 4.48 and 1.95 respectively，and the confidence intervals narrowed from （－0.44，1.97），（－1.01，0.03）to （4.24，4.72）and（1.90，2.01）respectively during 2004 to 2021，suggesting that the signals kept stable . CONCLUSIONS The risks of peripheral edema ，hypotension，arrhythmia，pulmonary edema ，gingival hyperplasia ，skin related ADE ，acute renal injury ， depression and suicide should be alert when using amlodipine and lercanidipine in clinic .

OBJECTIVE To excavate and evaluate β-blockers associated with acute renal failure（ARF）signal. METHODS Using the report odds ratio （ROR）method and Bayesian confidence interval progressive neural network （BCPNN）method，signal detection and analysis were performed for 4 kinds of β-blockers（metoprolol，bisoprolol，atenolol，nebivolol）associated with ARF Δ 基金项目：重庆市临床药学重点专科建设项目 （No.渝卫办发 in FDA adverse event reporting system （FAERS）from the two 〔2020〕68号）；重庆医科大学未来医学青年创新团队发展支持计划项 dimensions of Standard International Dictionary of Medical 目（No.W0081） Terms （MedDRA） analysis query （SMQ） term set and ＊药师，硕士研究生。研究方向：药物警戒。电话：023-68485161。 preferred term （PT） level terms. When the two methods E-mail：2020121624@stu.cqmu.edu.cn detected positive signals at the same time ，it indicated that # 通信作者：主任药师，硕士生导师。研究方向：临床药学、药物警 suspicious signals were detected. RESULTS Totally 14 328 戒。电话：023-63625666。E-mail：jiayuntaomail@hospital.cqmu.edu.cn ARF reports of 4 kinds of β-blockers were retrieved within the ·1380· China Pharmacy 2022Vol. 33 No. 11 中国药房 2022年第33卷第11期 narrow sense of “acute renal failure ”in SMQ term set ，of which men （6 964）were more than women （6 206）. The age of patients was mainly concentrated in the middle-aged and elderly （≥45 years old ），and serious adverse events accounted for 77.23％. The results of signal retrieval based on SMQ term set showed that ROR values and 95％ confidence intervals of metoprolol ，bisoprolol， atenolol and nebivolol detected by ROR method were 2.58（2.51，2.65），5.30（5.14，5.47），2.80（2.69，2.91）and 3.28（3.04， 3.53）respectively. The signal components （IC）detected by BCPNN method and the lower limit of IC were 1.29（1.25），2.26 （2.22），1.42（1.36）and 1.64（1.53）respectively，suggesting suspicious signals were detected in these four kinds of β-blockers associated ARF. The results of signal detection based on PT level terms showed that 37 positive signals were detected by ROR method，38 positive signals were detected by BCPNN method ，and 36 suspicious signals were detected by the two methods at the same time. For each drug ，12 suspicious signals of metoprolol were detected at the same time ，9 suspicious signals of bisoprolol and atenolol were detected at the same time ，and 6 suspicious signals of nebivolol were detected at the same time ；the number and type of signals were different among the 4 kinds of drug. CONCLUSIONS Four kinds of β-blockers may cause ARF. Compared with metoprolol and atenolol ，bisoprolol and nebivolol have strong statistical correlation with ARF ，suggesting that medical personnel should pay attention to the possible renal related adverse reactions of these drugs in the process of clinical use.