BackgroundMedulloblastoma (MB) is the most common malignant pediatric brain tumor, yet systematic studies on molecular characteristics and treatment efficacy in Chinese pediatric MB remain scarce. This study evaluates recurrence and mortality risk factors and the feasibility of intensified chemotherapy.MethodsA retrospective analysis of 381 MB patients (WNT: 63, SHH: 106, Group 3: 27, Group 4: 185) was conducted. Kaplan-Meier analysis estimated survival rates, and Cox regression identified independent risk factors for recurrence and mortality.ResultsWith a median follow-up of 4.8 years, 5-year PFS and OS were 69.9% ± 2.4% and 80.6% ± 2.1%, respectively. WNT-MB had the best prognosis, while Group 3-MB had the worst. Independent recurrence risk factors included high-risk status (HR=2.931, p<0.001), TP53 mutation (HR=1.873, p<0.001), MYCN amplification (HR=1.52, p=0.001), chromosome 12p amplification, and 9q deletion. Mortality was associated with LC/A pathology (HR=1.573, p=0.007), TP53 mutation (HR=2.049, p<0.001), and high-risk status (HR=3.966, p<0.001). TP53 mutations influenced WNT-MB recurrence, and Group 3-MB showed a high recurrence risk even without MYC amplification or metastasis. No treatment-related fatalities were observed.ConclusionThis study identified key clinical and molecular risk factors associated with recurrence and mortality in pediatric medulloblastoma. The findings underscore the prognostic relevance of TP53 mutations, MYCN amplification, and specific chromosomal alterations, particularly in non-metastatic subgroups. These insights may help guide risk-adapted and personalized treatment strategies in future studies.

ObjectiveTumor-associated macrophages (TAMs) constitute a significant proportion of the immune cell population within brain tumors. The polarization of macrophages exerts an important influence on the tumor microenvironment (TME). Nevertheless, the specific role of TAMs in sonic hedgehog (SHH) medulloblastoma remains unclear. To investigate the polarization characteristics and effects of TAMs in SHH medulloblastoma, we evaluated the infiltration of M1 and M2 macrophages in SHH medulloblastoma tissues and analyzed the correlation between TAMs recruitment and the clinical outcome of SHH medulloblastoma patients.MethodsWe enrolled a total of 42 patients diagnosed with SHH medulloblastoma. Using multiple immunofluorescence staining on paraffin-embedded sections, we detected the activated phenotype (M1/M2) by monoclonal antibodies for CD68, HLA-DR and CD163. Subsequently, we analyzed the correlation between TAMs and clinical characteristics as well as prognostic factors.ResultsThe median age of 42 patients (31 boys, 11 girls) was 5.3 years (range: 0.8-15.1 years). All patients had confirmed pathological types, including 4 cases of classic medulloblastoma (CMB), 33 cases of desmoplastic/nodular medulloblastoma (DNMB), 3 cases of medulloblastoma with extensive nodularity (MBEN), and 2 cases of large-cell/anaplastic medulloblastoma (LCA). Thirteen cases presented with metastasis at diagnosis, while twenty-nine cases were without metastasis. Four cases had high-risk genetic abnormalities. Different proportions of macrophages were found in the collected medulloblastoma tissues, and large amounts of CD68+HLA-DR+CD163+ cells were found. The study revealed that Mtotal (total macrophages) and Mmix (CD68+HLA-DR+CD163+ cells) were significantly higher in group of patients <5 years old (P < 0.05), and Mtotal in non-metastatic group were significantly higher than that in metastatic group (P = 0.043). M2 macrophages in CMB group were significantly higher than that in DNMB/MBEN group (P = 0.036), M1 macrophages were significantly higher in children without high-risk genetic abnormalities (P = 0.007). Five-year PFS was significantly poorer in patients ≥5 years old and metastatic group (P < 0.05). High Mtotal group had a better 5-year PFS (P = 0.000), whereas high M2 group had both better 5-year PFS and OS (P = 0.001, P = 0.001). Multivariate analysis showed that Mtotal and M2 macrophages were independent prognostic factors for 5-year PFS, and M2 macrophages were an independent prognostic factor for 5-year OS.ConclusionThe increase in total macrophages and M2 macrophages predicts a better outcome of SHH medulloblastoma. TAMs especially M2 macrophages might be a therapeutic target for SHH medulloblastoma.

OBJECTIVES:To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS:A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS:Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS:Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.

Objective:T cells and tumor-associated macrophages (TAMs) are critical immune components within the brain tumor microenvironment (TME), yet their precise roles in medulloblastoma remains unclear. In this study, we examined the infiltration characteristics of T cells in medulloblastoma tissues and analyzed the correlation between T cells and the clinical outcomes of medulloblastoma patients. Additionally, we further investigated the relationship between T cells and TAMs. Methods:We enrolled a total of 72 patients diagnosed with medulloblastoma and subsequently detected the T cell makers and programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) in paraffin-embedded sections using multiple immunofluorescence staining method. The correlation between T cell infiltration, clinical characteristics and prognosis were analyzed. Finally, we used Spearman correlation analysis to evaluate the correlation between T cells and TAMs. Results:The median age at diagnosis of 72 patients (54 boys, 18 girls) was 7.5 years (range: 0.8-18 years). These patients included 43 cases of classic medulloblastoma (CMB), 24 cases of desmoplastic/nodular medulloblastoma (DNMB), 2 cases of medulloblastoma with extensive nodularity (MBEN) and 3 cases of large-cell/anaplastic medulloblastoma (LCA). The molecular subgroups consisted of 3 wingless (WNT), 29 sonic hedgehog (SHH) and 40 non-WNT/non-SHH cases. Twenty-five cases presented with metastasis at diagnosis, while 47 cases were without metastasis. Thirteen cases exhibited with high-risk genetic abnormalities. The total T cells (P = 0.031) and CD4 T cells (P = 0.045) were significantly elevated in the SHH subgroup compared to those in the non-WNT/non-SHH subgroup. Patients with increased CD4 T cells had better 5-year PFS (P = 0.000) and OS (P = 0.001), while patients without metastasis showed better 5-year PFS (P = 0.031) and OS (P = 0.015). Multivariate analysis showed that CD4 T cells were an independent prognostic factor affecting both the 5-year PFS (P = 0.004, HR = 0.230, 95% CI = 0.085-0.662) and OS (P = 0.017, HR = 0.180, 95% CI = 0.044-0.739). Additionally, it was observed that CD4 T cells exhibited a positive correlation with Mtotal (total macrophages) (P < 0.05, r = 0.249) and Mmix (M1/M2 mixed phenotype macrophages) (P < 0.01, r = 0.325), and CD3+CD8+PD-1+ cells showed a positive correlation with Mmix (P < 0.05, r = 0.258). Conclusion:The increase in CD4 T cells predicts a better prognosis in medulloblastoma patients, particularly within the SHH and non-WNT/non-SHH subgroups, and they may serve as a potential therapeutic target for medulloblastoma. Additionally, there may be a potential interaction between CD4 T cells and TAMs that warrants further investigation.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome. The widely used HLH-1994/2004 protocols are primarily designed for primary HLH (pHLH). However, in Asia, particularly in China, secondary HLH (sHLH) is more prevalent, which may limit the efficacy of these protocols and increase treatment-related toxicity. To address this, we conducted a multicenter, prospective, single-arm clinical study to evaluate the CCHG-HLH-2018 protocol, a stratified treatment regimen based on glucocorticoids and etoposide, for pediatric HLH patients in China. A total of 286 patients from 20 centers were included, with a median follow-up of 64 months. Based on HLH-related indicators at onset, 64 patients (22.4%) were classified as low-risk group and 222 (77.6%) as high-risk group. The 5-year overall survival (OS) for all patients was 86.3% (95% CI, 81.7-89.8), with 96.9% (95% CI, 88.1-99.2) in low-risk group and 83.2% (95% CI, 77.6-87.5) in high-risk group (Holm-Bonferroni adjusted p = 0.006). The 5-year OS for pHLH patients was 72.9% (95% CI, 58.0-83.3), significantly lower than the 89.0% (95% CI, 84.3-92.4) for sHLH patients (Holm-Bonferroni adjusted p = 0.008). Among all patients, 54 (18.9%) achieved sustained remission without chemotherapy. No significant differences in OS and EFS were observed between high-risk patients receiving CSA-containing regimens and those receiving non-CSA regimens (p = 0.148, p = 0.107). However, exploratory subgroup analysis of idiopathic HLH patients suggested a trend toward improved survival with the CSA-containing regimen. The safety profile of the CCHG-HLH-2018 protocol was acceptable, with fewer adverse events in the low-risk group. Our findings suggest this stratified protocol is effective in reducing chemotherapy intensity for Chinese children with HLH. Trial Registration: http://www.chictr.org.cn, identifier: ChiCTR1800017267.

Abstract OBJECTIVE To explore the clinical characteristics of pediatric recurrent pineoblastoma in Beijing. METHODS Eighteen patients with newly diagnosed pineoblastoma were admitted to Beijing Shijitan Hospital between January 2014 and December 2022. The clinical data were retrospectively analyzed. RESULTS Among the 18 patients (M/F=8:1), all were treated with surgery, and both radiotherapy and chemotherapy were administered. Nine patients experienced recurrence, and 2 patients died at last follow-up. The Median follow-up time were 56 months. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) were (42.0±13.1) %, and (88.1±7.9) %, respectively. Among the 9 recurrent patients, one was < 3 years, and 8 cases ≥ 3 years. One girl and 8 boys relapsed; 7 cases were M0 and 2 with metastases at diagnosis; 7 cases were GTR; Two cases experienced recurrence within one year (10 months each), and one died. The other 7 patients relapsed after one year, the median time to first relapse were 24.0 (range: 10.0~49.0)months. The sex, age group, metastases at diagnosis, GTR or not, recurrent sites were not significantly affects PFS. Although the 9 recurrent patients received both cerebral and spinal irradiation and chemotherapy followed by surgery, the different order of chemotherapy or radiotherapy first were significantly affected the duration of remission. The median time before the first relapse after surgery was longer in those who treated under the order of craniospinal irradiation followed by chemotherapy than those of the inverse order (29m vs 13m, χ2=6.528, P=0.011). In addition, one case with germline mutation of Dicer1, experienced recurrences more than 3 times although received second surgery and second radiotherapy, and multiple cycles of chemotherapy in our center, which indicates poorer outcome. CONCLUSION Pineoblastoma is rare and prone to relapse, the order of chemotherapy first may have shorter remission time before the first recurrence after surgery (P< 0.05).

Background The protective effects of metformin (Met) against doxorubicin (Dox)-induced cardiotoxicity via potential hypotheses of mechanisms of action with unknown reliability and credibility.Objectives This study aimed to investigate the protective effects of Met against Dox-induced cardiotoxicity and the underlying mechanisms of action, as well as examine their reliability and credibility.Methods A comprehensive search was conducted within the PubMed, Embase, Web of Science, Science Direct, Scopus, and CNKI databases from inception to 31 December 2023. Animal experiments evaluating the efficacy of Met against Dox-induced cardiotoxicity were included in this study. The primary efficacy outcomes were markers of myocardial injury. Effect size was measured using the standardized mean difference for continuous variables. Data were pooled using a random-effects model in the Stata 18 statistical software package.Results Twenty-one studies involving 203-208 animals treated with Dox and 271-276 animals treated with Dox and Met were included in this analysis. Quality assessment revealed high-quality scores. Pooled results favored Met treatment based on the serum lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI), and aspartate aminotransferase levels. Sensitivity analysis using the leave-one-out method demonstrated stable results. Funnel plots, Egger's test, and Begg's test confirmed potential publication bias. The oxidative stress hypothesis has been investigated extensively based on abundant evidence.Conclusion Met is effective and safe for protecting against Dox-induced cardiotoxicity, thus making it an appropriate drug for clinical investigation. The oxidative stress hypothesis of mechanism of action is well established with highest reliability and credibility.

The incidence of type 2 diabetes is high, and the existing metformin hydrochloride (MH) tablets of 250 mg cannot meet the demands of the Chinese drug market. This study aimed to evaluate the bioequivalence and safety of generic formulations of MH tablets (test formulation [T], 250 mg/tablet) and innovative products (reference formulation [R], 250 mg/tablet) under fasting conditions. This was an open-label, single-dose, 2-period, 2-sequence crossover, single-center, randomized phase I clinical trial. T and R were considered bioequivalent if the adjusted geometric mean ratios (GMRs) and 90% confidence intervals of the area under the curve (AUC) and maximum concentration (Cmax ) were within the range of 0.8-1.25. Thirty-five participants completed the trial. The T/R adjusted GMRs (95.7% for Cmax , 98.7% for AUC0→t , 98.8% for AUC0→∞ ) were within the acceptable bioequivalence range of 80%-125%. No serious adverse events or suspected or unexpected serious adverse reactions occurred during this trial. The study findings confirmed that generic MH is a well-tolerated and bioequivalent alternative to innovative products under fasting conditions in healthy Chinese participants. (www.chinadrugtrials.org.cn; registration no. CTR20190356).

BACKGROUND:A phase II clinical trial of metformin (MET) for the treatment of doxorubicin (DOX)-induced cardiotoxicity (NCT02472353) failed. OBJECTIVES:The aims of this study were to confirm MET-mediated protection against DOX-induced cardiotoxicity and its mechanism using H9C2 cells, and to establish a Wistar rat model of DOX-induced cardiotoxicity. Subsequently, Wistar rats were utilized to identify clinically relevant indicators for evaluating MET-mediated protection against DOX-induced cardiotoxicity, thereby facilitating early transition towards successful clinical trials. METHODS:MET-mediated protection was assessed using cell viability and cytotoxicity experiments. Additionally, intramitochondrial reactive oxygen species (ROS) levels were measured using an ROS fluorescent probe (dihydroethidium) to confirm the oxidative stress mechanism. Eighteen Wistar rats were randomly allocated to the control, DOX, and DOX+MET groups; and the body weight, adverse drug reactions (ADRs), myocardial injury, cardiac function, oxidative stress, and histopathology of heart tissues were compared between groups. RESULTS:H9C2 cells treated with MET/Dexrazoxane demonstrated dose-dependent protection against DOX-induced cardiotoxicity. The fluorescence intensity of H9C2 cells suggested DOX-induced cardiomyocyte toxicity and MET-mediated protection against DOX-induced cardiotoxicity. In vivo experiments confirmed that a rat model of DOX-induced cardiotoxicity was successfully established, but MET-mediated protection against DOX-induced cardiotoxicity was not demonstrated. This was attributed to insufficient energy intake because of ADRs, such as vomiting. CONCLUSIONS:We confirmed the MET-mediated protection against DOX-induced cardiomyocyte toxicity and its mechanism involving the inhibition of oxidative stress in vitro experiments. It is imperative to investigate the optimal conditions for MET-mediated protection against DOX-induced cardiotoxicity in vivo or clinical trials.

The incidence of type 2 diabetes is high, and the existing metformin hydrochloride (MH) tablets of 250 mg cannot meet the demands of the Chinese drug market. This study aimed to evaluate the bioequivalence and safety of generic formulations of MH tablets (test formulation [T], 250 mg/tablet) and innovative products (reference formulation [R], 250 mg/tablet) under fasting conditions. This was an open-label, single-dose, 2-period, 2-sequence crossover, single-center, randomized phase I clinical trial. T and R were considered bioequivalent if the adjusted geometric mean ratios (GMRs) and 90% confidence intervals of the area under the curve (AUC) and maximum concentration (Cmax) were within the range of 0.8-1.25. Thirty-five participants completed the trial. The T/R adjusted GMRs (95.7% for Cmax, 98.7% for AUC0 -> t, 98.8% for AUC0 ->infinity) were within the acceptable bioequivalence range of 80%-125%. No serious adverse events or suspected or unexpected serious adverse reactions occurred during this trial. The study findings confirmed that generic MH is a well-tolerated and bioequivalent alternative to innovative products under fasting conditions in healthy Chinese participants. (; registration no. CTR20190356)

Cancer patients are at high risk of developing venous thromboembolism (VTE). The risk of VTE could be mitigated with the administration of prophylactic anticoagulants. Therefore, risk assessment models would be a useful tool in order to identify those patients who are at higher risk and will be benefited more by prophylactic anticoagulants. This study retrospectively examined 528 newly diagnosed colorectal cancer patients from January 2019 to January 2021. Specified logistic regression models were employed to screen the factors and establish prediction tools based on nomograms according to the final included variables. Discrimination, calibration, and clinical applicability were used to assess the performance of screening tools. In addition, internal verifications were conducted through 10-fold cross-verification, leave-one-out cross-validation, and Bootstrap verification. Four risk factors, closely related to the occurrence of VTE in colorectal cancer patients, were identified after univariate and multivariate logistic regression, including age, body mass index, activated partial thromboplastin time, and D-Dimer value. Besides, the risk assessment model named ABAD was built on the basis, displaying good discriminations and calibrations. The area under the curve was 0.705 (95% confidence interval [CI], 0.644 to 0.766). According to Hosmer–Lemeshow goodness-of-fit test, a good agreement between the predicted and observed VTE events in patients with newly-diagnosed gastrointestinal cancer was observed for χ2 = 6.864, P = .551. Internal validation was applied with a C-index of 0.669 in the 10-fold cross-verification, 0.658 in the leave-one-out cross verification and 0.684 in the bootstrap verification. We developed a prediction model called ABAD for newly diagnosed colorectal cancer patients, which can be used to predict the risk of VTE. After evaluation and internal verification, we believe that ABAD exhibited high predictive performance and availability and could be recommended.

评价盐酸二甲双胍缓释片受试制剂和参比制剂在健康受试者餐后单次给药条件下的生物等效性和安全性.试验采用单中心、随机、开放、单剂量、两周期、两序列、双交叉设计,32例健康受试者在餐后状态下单次服用受试制剂或参比制剂0.5 g,在给药前(0 h)至给药后1、3、4、4.5、5、5.5、6、7、8、9、10、12、15、24、36和48 h采集静脉血4 mL,检测血浆样本中二甲双胍的浓度,用Win Nonlin 7.0软件计算药代动力学参数,当受试制剂与参比制剂的cmax、AUC0-t、AUC0-∞几何均值比的90％置信区间均在80.00％ ～125.00％等效区间内,证明两制剂生物等效.有1例受试者因不良事件脱落.受试制剂和参比制剂的主要药代动力学参数:cmax为(0.68±0.14)和(0.65±0.11)mg/L,AUC0-t为(7.33±1.65)和(7.00±1.89)h·mg/L,AUC0-∞为(7.39±1.67)和(7.06±1.91)h·mg/L;二者cmax、AUC0-t和AUC0-∞几何均值比的90％置信区间分别为101.45％ ～109.14％、100.08％ ～112.32％和100.24％ ～112.28％,均在80.00％ ～125.00％生物等效区间内.试验过程中无严重不良事件和非预期不良事件发生.结果表明,盐酸二甲双胍缓释片受试制剂和参比制剂在健康受试者中餐后单次给药条件下生物等效,二者安全性和耐受性好.

背景 儿童脉络丛癌(CPC)临床罕见,国内报道较少.目的 探讨儿童CPC的临床特征、治疗及结局.设计 病例系列报告.方法 回顾性分析首都医科大学附属北京世纪坛医院儿科于 2017 年 1 月至 2022 年 10 月收治的手术后病理确诊的CPC患儿,随访截至 2022 年12 月31 日.截取患儿性别、诊断年龄、临床表现、治疗和随访情况,生存数据采用Kaplan-Meier法分析.主要结局指标 总体生存期(OS)和无进展生存期(PFS).结果 12 例 CPC患儿纳入分析,男 4 例,女 8 例;中位诊断年龄 29.7(5.8～119.6)个月,起病年龄＜3 岁 8 例;肿瘤直径≥5cm8 例,＜5 cm 4 例;肿瘤位于幕上 9 例,幕下 3 例;肿瘤位于脑室系统 6 例,脑室外累及脑实质 6 例;起病时发现播散转移 2 例,无转移 10 例.12 例均接受肿瘤切除手术,全切 8 例,近全切 4 例.术后仅行化疗 5 例(42％),联合放射治疗及化疗 7 例(58％).截至末次随访,8 例出现肿瘤复发或进展,其中 4 例因肿瘤进展后死亡.平均 OS(56.7±8.8)个月,1、3、5 年 OS 率分别为(83.3±10.8)％、(66.7±13.6)％和(66.7±13.6)％.平均 PFS(24.3±7.2)个月,1、3 年 PFS 率分别为(41.7±14.2)％和(33.3±13.6)％.Kaplan-Meier单因素分析发现,肿瘤位于幕下 3 年OS低于幕上(χ2 =8.562,P=0.003);单纯化疗 3 年OS低于放化疗联合治疗(χ2=8.488,P=0.004);不同性别、起病年龄(＜3 岁与 3～18 岁)、肿瘤直径(≥5 cm与＜5 cm)、切除程度、有无转移、是否放化疗对 3 年PFS的影响差异均无统计学意义(P均＞0.05).结论 儿童CPC临床罕见,预后差,肿瘤位于幕下及单纯化疗为影响OS的不良预后因素.

Abstract OBJECTIVE To investigate the clinical features, treatment and outcome in pediatric choroid plexus carcinoma (CPC) patients. METHODS Twelve children with CPC confirmed by pathology who were admitted to Beijing Shijitan Hospital from January 2017 to October 2022, were included. The last follow-up was December 31, 2022. Kaplan-Meier method was adopted for survival analysis. RESULTS Among the 12 patients, 4 were males and 8 females. The median age at diagnosis was 29.7 (range, 5.8-119.6) months, with 8 cases less than 3 years old at the time of diagnosis. Nine cases were supratentorial, and 3 infratentorial. The tumor was located in ventricular system in 6 cases, external involvement of brain parenchyma in 6 cases. Two cases experienced metastases (M+) and 10 M0 at the time of diagnosis. All patients received tumor resection, with 8 cases GTR and 4 NTR. Five cases received chemotherapy only and 7 patients radio-chemotherapy after surgery. At last follow-up, 8 cases experienced tumor recurrence or progression, and 4 died. The mean OS were (56.7±8.8) months, The 1, 3, 5-year OS were (83.3%±10.8)%、(66.7%±13.6)%, and (66.7%±13.6)%, respectively. The mean PFS time were (24.3±7.2) months, The 1, 3-year PFS were (41.7%±14.2)% and (33.3%±13.6)%, respectively. Univariate analysis showed the OS were poorer in children with infratentorial tumors than supratentorial tumors (χ2 =8.562, P = 0.003). And the OS was also lower in patients who received chemotherapy only than those who received both radiotherapy and chemotherapy (χ2 =8.488, P =0.004). The difference in PFS between groups were not significant (P>0.05). CONCLUSION CPC is very rare and with poor prognosis in children. Children with infratentorial tumors and who received chemotherapy only tend to have poorer OS. Due to the small sample size, further clinical trials need to be developed to verify.

Objective:To explore the therapeutic efficacy and toxicity of oral Etoposide chemotherapy in children with disseminated medulloblastoma (MB) after the standard treatment plan.Methods:The clinical data of 86 children with disseminated MB admitted in the Department of Pediatrics, Beijing Shijitan Hospital of Capital Medical University from January 2016 to May 2020 were analyzed retrospectively.The median age of children was 8.8 (3.0-16.7) years old.Among them, 33 children treated with maintenance chemotherapy via oral Etoposide were included in the chemotherapy group, and 53 children without oral maintenance chemotherapy were included in the non-chemotherapy group.The gender distribution, surgical resection range, pathological type, molecular classification, postoperative mutism, M-stage and survival[progression-free survival (PFS) and overall survival (OS)] of the 2 groups were compared.The main adverse events of oral Etoposide chemotherapy were recorded. Chi- square test is used for data comparison, Kaplan-Meier method was used to plot the survival curve of disseminated MB patients, followed by the Log- rank test. Results:There were no significant differences in gender, surgical resection range, pathological type, molecular typing, postoperative mutism and M-stage between the 2 groups (all P>0.05). Of 86 patients, the median PFS and OS were 3.0 (0.2-6.3) years, and 3.6 (0.5-6.3) years, respectively.Twenty five cases (29.1%) relapsed, 13 cases (15.1%) died.The 3-year[(65.8±6.8)% vs.(82.0±7.3)%] and 5-year PFS[(56.8±7.7)% vs.(82.0±7.3)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.037). The 3-year[(81.6±5.6)% vs.100.0%] and 5-year OS[(71.2±7.7)% vs.(92.3±7.4)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.025). Among the children with the SHH subtype, the PFS of children with oral Etoposide maintenance chemotherapy after a regular treatment was significantly higher than that without oral maintenance chemotherapy (100.0% vs.57.1%)( P=0.021). The major adverse events of oral Etoposide were myelosuppression and gastrointestinal symptoms, which were mostly relieved after a symptomatic treatment.Treatment-related deaths were not reported. Conclusions:The prognosis of disseminated MB in children is relatively poor.Oral Etoposide for maintenance therapy after a standard treatment is beneficial in reducing relapse and improving the 5-year survival, which is well tolerated.

背景 目前对儿童颅内生殖细胞肿瘤(ICGCTs)的及时诊断仍面临困难.目的 分析ICGCTs患儿延迟诊断的影响因素.设计 病例对照研究.方法 纳入 2011 年 10 月至 2021 年 4 月在首都医科大学附属北京世纪坛医院就诊的ICGCTs患儿,发病至诊断时间≥6 个月为延迟诊断组,反之为无延迟诊断组.根据导致延迟诊断的原因将延迟诊断组进一步分为疾病原因亚组、家庭原因亚组和诊断原因亚组.截取患儿的一般信息、临床表现、辅助检查等临床资料,在两组间单因素有序Logistic回归分析的基础上行多元Logistic回归分析.主要结局指标 ICGCTs延迟诊断的影响因素.结果 158 例ICGCTs患儿纳入分析,男 114 例,女 44 例.无延迟诊断组 88 例,延迟诊断组 70 例,其中疾病原因亚组 15 例,家庭原因亚组 23 例,诊断原因亚组 32 例.起病症状:无延迟诊断组以高颅压三主征多见,疾病原因亚组和家庭原因亚组以内分泌症状多见,诊断原因亚组以神经精神症状和内分泌症状多见.诊断原因亚组以肿瘤多病灶为主,其余各组以单病灶为主.无延迟诊断组病理分型为非生殖细胞性的生殖细胞瘤(NGGCTs)、肿瘤最大直径≥3 cm、发生脑积水、需行脑室腹腔分流术/三脑室底造瘘术的患儿较多,β-HCG≥5 mIU·mL-1 在发病≥6 个月出现的患儿较少.进一步分析导致延迟诊断的危险因素后发现,内分泌症状是家庭原因亚组患儿延迟诊断的危险因素;诊断原因亚组中高颅压三主征、肿瘤最大直径≥3 cm是患儿延迟诊断的保护因素,β-HCG≥5 mIU·mL-1在发病≥6 个月出现是延迟诊断的危险因素.结论 ICGCTs的延迟诊断与疾病自身特征、患儿家庭认知和医院诊疗水平相关,需根据患儿具体情况制定个体化诊疗方案.

Background:Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population remains unclear; thus, we aimed to assess the proportion of hereditary thrombophilia via a meta-analysis.Methods:Publications from PubMed, EMBASE, web of science, and Cochrane before December 30, 2022, were searched. Studies from Japan, Korea, China, Hong Kong, Taiwan, Singapore, Thailand, Vietnam, Myanmar, and Cambodia were included. Congenital thrombophilia was described as diseases including protein C (PC) deficiency, protein S (PS) deficiency, antithrombin (AT) deficiency, factor (F)V Leiden (FVL), and prothrombin G20210A mutations. Studies were selected by 2 reviewers for methodological quality analysis. A random-effects model was used for the meta-analysis, assuming that estimated effects in the different studies are not identical.Results:Forty-four studies involving 6453 patients from 7 counties/regions were included in the meta-analysis. The prevalence of PC, PS, and AT deficiencies were 7.1%, 8.3%, and 3.8%, respectively. Among 2924 patients from 22 studies, 5 patients were carriers of FVL mutation. Among 2196 patients from 10 studies, 2 patients were carriers of prothrombin G20210A mutation in a Thailand study.Conclusion:The prevalence of PC, PS, and AT deficiencies was relatively high, while a much lower prevalence of FVL and prothrombin G20210A mutations were identified in East-Asian patients with VTE. Our data stress the relative higher prevalence of PC, PS, and AT deficiencies for thrombophilia in the East-Asian VTE population.

BackgroundThe efficacy and safety of percutaneous transluminal pulmonary angioplasty (PTPA) for Takayasu arteritis-associated pulmonary hypertension (TA-PH) remain unclear. ObjectivesTo examine the efficacy and safety of PTPA in TA-PH. MethodsPubMed, Embase, and the Cochrane Central Register of Controlled Trials Library were searched from inception to August 18, 2022, for articles investigating the efficacy and safety of PTPA for TA-PH. The primary efficacy outcomes were pulmonary vascular resistance (PVR) changes from baseline to re-evaluation and 6-minute walking distance (6MWD). The safety outcome was procedure-related complications. ResultsFive articles comprising 104 patients with TA-PH who underwent PTPA were included. The scores of article quality, as assessed using the methodological index for nonrandomized studies tool, were high, ranging from 13 to 15 points. The pooled treatment effects of PVR (weighted mean difference [WMD]: -4.8 WU; 95% confidence interval [CI]: -6.0 to -3.5 WU; I-2 = 0.0%), 6MWD (WMD: 101.9 m; 95% CI: 60.3-143.6 m; I-2 = 70.4%) significantly improved. Procedure-related complications, which predominantly present as pulmonary artery injury and pulmonary injury, occurred in 32.0% of the included patients. Periprocedural death occurred in one patient (1.0%, 1/100). ConclusionsPatients with TA-PH could benefit from PTPA in terms of hemodynamics and exercise tolerance, at the expense of procedure-related complications. PTPA should be encouraged to enhance the treatment response in TA-PH. These findings need to be confirmed by further studies, ideally, randomized controlled trials. RegistrationPROSPERO CRD42022354087.

Background: The effects of food on the pharmacokinetics and safety of metformin hydrochloride (MH) are unclear. Objective: To discover the effects of food on the pharmacokinetics and safety of MH, and its influence factors. Methods: English and Chinese databases, and grey (unpublished) literature were searched for eligible studies (registration No. CRD 42022321067 in PROSPERO network). The summary weighted mean difference for continuous variables, and the risk ratio for dichotomous variables was calculated for the main pharmacokinetic parameters. Heterogeneity among the included studies was analyzed using the I-2 test. Subgroup analyses, meta-regression, sensitivity analysis, and publication bias test were conducted. Results: Fourteen clinical trials were included, comprising 408 participants. The pooled AUC(0 -> t), AUC(0 ->infinity), and C-max were decreased by about 30.21% (I-2 = 16.7%, p = 0.276), 28.00% (I-2 = 73.6%, p < 0.001), and 40.38% (I-2 = 92.8%, p < 0.001). T-max was delayed by about 29.42% (I-2 = 45.1%, p = 0.034). Subgroup analysis and meta-regression analysis revealed dosage of MH and gender composition as two significant sources of heterogeneity in AUC(0 ->infinity) and C-max. Sensitivity analysis indicated that most of results were stable. The Egger's regression test and the Begg test (p > 0.05) confirmed that there is no publication bias. Conclusions: Pharmacokinetics parameters of MH were affected by food. High-fat, high-calorie diet lowered the extent and rate of absorption while slowing the absorption of metformin. These findings suggest that it is necessary to increase the dosage of MH in order to maintain the same treatment effect when administration of MH after a high fat, high calorie

Background As per the National Medical Products Administration (NMPA) requirements, the quality and efficacy of generic drugs must be consistent with those of the innovator drug. We aimed to evaluate the bioequivalence and safety of generic metformin hydrochloride sustained-release (MH-SR) tablets (Boke®) developed by Beijing Wanhui Double-crane Pharmaceutical Co. Ltd., China and the innovator product metformin hydrochloride extended-release tablets (Glucophage®-XR) manufactured by Bristol-Myers Squibb Company, New York, NY, in healthy Chinese volunteers.Materials and methods We performed a bioequivalence and safety assessment of MH-SR (500 mg/tablet) and Glucophage®-XR (500 mg/tablet) tablets in a randomized, open-label, two-period, two-sequence crossover, single-dose oral study in 48 healthy Chinese adult participants under fasting conditions (Chinese Clinical Trial Registration No. CTR20171306). The washout period was seven days. Bioequivalence (80.00–125.00%) was assessed using adjusted geometric mean ratios (GMRs) and two-sided 90% confidence intervals (CIs) of the area under the curve (AUC) and maximum concentration (Cmax) for each component.Results The 90% CIs of the test/reference preparation for key pharmacokinetic parameters were 97.36–108.30% for AUC0→t, 97.26–108.09% for AUC0→∞ and 96.76–111.37% for Cmax. No severe adverse events (AEs) were observed. However, 38 adverse drug reactions (ADRs) occurred, including metabolic or nutritional conditions (n = 8), infections (n = 2), gastrointestinal conditions (n = 10) and abnormal inspection (n = 18). No significant difference was observed between MH-SR (23 ADRs, 10 participants) and Glucophage®-XR (15 ADRs, 12 participants) (p = .500). Bioequivalence was concluded since the 90% CIs of the main pharmacokinetic parameters were within the equivalence interval (80.00–125.00%).Conclusions MH-SR (500 mg/tablet) and Glucophage®-XR (500 mg/tablet) were found to be bioequivalent and safe under fasting conditions in healthy Chinese participants. Thus, the market demand for MH-SR tablets (500 mg/tablet) can be met using the generic alternative.KEY MESSAGESGeneric MH-SR tablets (500 mg, Beijing Wanhui Double-crane Pharmaceutical Co. Ltd., Beijing, China) and innovator MH-SR tablets (Glucophage®-XR, 500 mg, Bristol-Myers Squibb Company, New York, NY, USA) were bioequivalent and safe in healthy Chinese volunteers under single-dose administration and fasting conditions.The main goal of this study is to support an increase in the supply of MH-SR tablets in China by proving the efficacy and safety of a generic alternative.Although no sugar was administered in the BE trial of the MH-SR tablets under fasting conditions, no hypoglycaemic event occurred. The method used in this study is expected to serve as a reference for BE studies of different MH-SR formulations.