Expression of p-AKT and p-mTOR in pediatric Burkitt lymphoma and their correlation with prognosis / 中华病理学杂志

To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance. Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children's Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis. A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (0.759, 0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (0.011, 0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (0.006, 0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% . 94.7%, (2)=4.123, 0.042) and PFS (5-year estimate, 66.7% . 94.7%, (2)=5.822, 0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group ((2)=4.881, 0.027); however, there was no statistical significance in 5-year PFS rate (0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% . 95.7%, (2)=6.285, 0.012; PFS: 65.5% . 91.3%, (2)=5.405, 0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL. The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

The roles of m6A in cancer biology and its targeted therapy / 药学学报

N6-methyladenosine (m6A) modification is one of the most common modifications of eukaryotic mRNA, and has become a hotspot in the field of life sciences in recent years. m6A modification is dynamically reversible in mammalian cells and regulated by m6A methyltransferase (writers), demethylase (erasers), and "reader" proteins. m6A can regulate various biological processes of mRNA such as RNA splicing, nuclear export, protein translation and degradation. Recent studies indicated that m6A is important for the initiation and development of cancer. The present review summarized biological functions of m6A on mRNA and discussed its roles in cell proliferation, migration, invasion, cell mentalism, and angiogenesis. Further, the m6A can regulate the development of various cancers including acute myelocytic leukemia (AML), breast, liver and colorectal cancer. Nowadays, the inhibitors of m6A related enzymes including fat-mass and obesity-associated protein and AlkB homolog 5 are being developed. We further discussed the potential values of m6A and its related targets on cancer therapy and treatment.

Cytogenetic characteristics of 163 children with acute lymphoblastic leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To further understand the cytogenetic characteristics of pediatric acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>Cytogenetic abnormalities of 163 children with newly diagnosed ALL (0-17 years of age) were evaluated by conventional cytogenetic analysis and fluorescent in situ hybridization findings.</p><p><b>RESULTS</b>Chromosome abnormalities were detected in 87.7% of patients (143/163). The ploidy levels most frequently observed among ALL patients were high hyperdiploidy (51-67 chromosomes) (45 cases, 27.6%), Chromosomes X and 21 were gained in 100% of these cases. The most common genetic alterations were t(12;21)/ETV6/RUNX1 (26 cases, 16.0%), followed by t(1;19)/TCF3/PBX1 (13 patients, 8.0%), t(4;11)/MLL rearrangement and t(8;14) IGH/MYC (6 cases, 3.7%), t(9;22)/BCR/ABL(2 cases, 1.2%), and iAMP21 (1 patient, 0.6%). The no-classical structural abnormalities included dup(1q) in 20.2%, del(6q) and del(9p) in 10.4%, del(12p) in 12.9% and del(13q) in 5.5%. The incidences of t(12;21), t(1;19), t(9;22) and high hyperdiploidy were consistent with reports in Western children (P>0.25). The incidence of (9;22) seemed to be much lower in our study than that in Korea (1.5% vs 9.5%, P<0.005).</p><p><b>CONCLUSION</b>Cytogenetic findings of childhood ALL patients are similar to that of Western countries, it seems no more adverse risk factors.</p>

Effects of carbamazepine on plasma concentrations of valproic acid and its toxic metabolite in epileptic patients / 药学学报

To investigate the effects of carbamazepine (CBZ) on the plasma concentrations of valproic acid (VPA) and its toxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in epileptic patients, the plasma concentrations of VPA and 4-ene VPA were determined, and the effect of CBZ on pharmacokinetics of VPA was evaluated. All patients had been divided into two groups (VPA group, n = 87; and VPA+CBZ group, n = 19). As compared to VPA group, the combination of CBZ significantly (P < 0.01) decreased the trough concentration of VPA [VPA group, (69.5 +/- 28.8) microg x mL(-1); VPA+CBZ group, (46.3 +/- 25.6) microg x mL(-1)] and does-adjusted VPA trough concentration [VPA group, (4.89 +/- 2.21) microg x mL(-1) x mg(-1) x kg(-1); VPA+CBZ group, (3.14 +/- 1.74) microg x mL(-1) x mg(-1) x kg(-1)]. However, the addition of CBZ did not influence the concentration of 4-ene VPA. The present study revealed that coadministration of CBZ can reduce VPA plasma concentration and may impact VPA clinical effect, therefore therapeutic drug mornitoring of VPA should be used when combined use of CBZ and VPA.

Diagnostic value of 64-slice spiral CT angiography in the diagnosis of multiple intracranial aneuysms: A report of 25 cases / 解放军医学杂志

Obbjective To evaluate the diagnostic value of 64-slice spiral CT angiography (CTA) in multiple intracranial aneurysms (MIA). Methods Twenty-five patients (9 males and 16 females, aged from 17 to 68 years) with suspected MIA underwent 64-slice spiral CTA with slice thi ckness of 0.625mm. The data of all patients were reconstructed with multiplanar reconstruction (MPR), 3-dimensional shade surface display (3-SSD), volume rendering (VR) and maximum intensity projection (MIP). The clinical diagnostic value was evaluated with the results of surgery or interventional embolization therapy. Results A total of 61 aneurysms were detected by 64-slice spiral CTA in 25 patients, among them 17 patients were with 2 aneurysms, 6 patients with 3 aneurysms, 1 patient with 4 aneurysms and 1 patient with 5 aneurysms. The 64-slice spiral CTA could not only clearly demonstrate MIA, but also the size, neck, axis point and parent artery of each aneurysm, and the spatial relationship between aneurysm and the adjacent vessels and bone structures. Twenty-one patients underwent microsurgery and four underwent embolization, the location, size and shape of aneurysm and its spatial relationship with adjacent structures were in accordance with the findings of 64-slice spiral CTA. Conclusion The 64-slice spiral CTA could be used as the first choice in the diagnosis of MIA for its high accuracy, and may be an important adjunct to digital subtraction angiography (DSA) in MIA treatment.

Comparison of the efficacy of CCCG-97 and BFM-90 protocols in the treatment for children with mature B-cell non-Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to evaluate the efficacy and toxicity of the CCCG-97 and BFM-90 protocols in the treatment of pediatric patients with B-cell non-Hodgkin's lymphoma (B-NHL) retrospectively, and to explore the optimal therapeutic strategy.</p><p><b>METHODS</b>Forty-five consecutive untreated patients (age of 18 years or less) with newly diagnosed B-NHL (including Burkitt Lymphoma and diffuse large B-cell lymphoma), treated in our hospital between July 1999 and December 2008 were enrolled in this study. The patients were classified into 2 groups by different protocols. From July 1999 to December 2004, twenty-one 3- to 13.8-year-old children were enrolled in the CCCG-97 group, with 1 in stage I/II, and 20 in stage III/IV(St Jude staging). From January 2005 to December 2008, twenty-four 2.8- to 14.1-year-old cases were enrolled in the BFM-90 group, with 3 in stage I/II, and 21 in stage III/IV (St Jude staging). The survival rates were evaluated by Kaplan-Meier analysis.</p><p><b>RESULTS</b>Forty of the 45 patients (88.9%) reached complete response (CR) after 2 courses of chemotherapy. In the CCCG-97 group, the CR rate was 95.2% (20/21 pts), while that in the BFM-90 group was 83.3% (20/24 pts). At a median follow-up time of 62 (17 to 131) months, the 5-year event-free survival (EFS) was 71.8% for all patients, and 69.1% for Stage III/IV, respectively. In the CCCG-97 group, the 3-year EFS was 76.2%. In the BFM-90 group, it was 75.0%. There was no significant difference in survival rates between the CCCG-97 and BFM-90 groups (P=0.975). Unfavorable events recorded were as follows: Death of progression before achieving CR during induction therapy in 4 cases, and relapse after achieving CR in 6 cases. The relapse rates were 19.0% (4/21 pts) in the CCCG-97 group and 8.3% (2/24 pts) in the BFM-90 group, with a non-significant statistical difference (P=0.292). Major toxicities were myelosuppression and mucositis, especially in the BFM-90 group, but were tolerable and manageable. five patients in the BFM-90 group received rituximab, 2 patients (Stage III) achieved CR, while the other 3 patients (Stage IV) had progressive disease or relapse.</p><p><b>CONCLUSIONS</b>Short-pulse and intensive chemotherapy, stratified according to stage of disease, can improve the survival rate of pediatric mature B-NHL. The efficacy of the CCCG-97 protocol and BFM-90 protocol is comparable and the toxicity is tolerable.</p>

Relationship between Willis circle variation and the occurrence of anterior and posterior communicating artery aneurysms investigated by 64-slice CT angiography / 中国脑血管病杂志

Objective: To investigate the relationship between the dysplasia of horizontal segment (A1 segment) of anterior cerebral artery and the formation of anterior and posterior communicating artery aneurysms. Methods: The data of 64-slice computed tomography angiography (CTA) of 216 patients were analyzed retrospectively. Of the 216 patients, CTA found 126 patients with aneurysm. They were divided into anterior communicating artery aneurysm (ACoAA) group (n = 69) and posterior communicating artery aneurysm (PCoAA) group (n = 57 ). The other patients without aneurysm revealed by CTA but with headache and dizziness (n = 90) were used as a control group. The presence or absence of aneurysm, the location, shape, size and neck width of aneurysm, the apex pointing of aneurysm as well as the relationship between the aneurysmal bodies and surrounding structures were analyzed. The prejudged results and the surgical results were compared. Whether the anterior cerebral artery A1 segment had dysplasia or not and whether it had fetal-type posterior cerebral artery or not were observed at the same time. Results: Circled digit oneA total of 126 patients with communicating artery aneurysm were revealed by 64-slice CTA, among them 69 were ACoAA and 57 were PCoAA. Taking DSA and surgery as determining standards, the sensibility and specificity detected by 64-slice CTA were 100%. Circled digit twoUnilateral hypoplasia or absence of A1 segment of anterior cerebral artery reached 81.7% in the ACoAA group, which was significantly higher than that in the PCoAA group or the control group (P < 0.05); fetal-type posterior cerebral artery in the PCoAA group reached 56.1% , which was significantly higher than that in the ACoAA group or the control group (P < 0.05). Conclusion: 64-slice CTA has higher sensibility and specificity for detecting cerebral aneurysms. Unilateral hypoplasia or absence of A1 segment of anterior cerebral artery and fetal-type posterior cerebral artery are closely associated with the occurrence of intracranial communicating artery aneurysms.

Clinical characteristics of hepatic veno-occlusive disease in 6 children with hematologic neoplasm treated with 6-thioguanine / 中华儿科杂志

<p><b>OBJECTIVE</b>To improve the treatment of drug related childhood hepatic veno-occlusive disease (HVOD), clinical characteristics of 6 children with hematologic neoplasm from 2 hospitals of China Children's Leukemia Group (CCLG) treated with 6-thioguanine (6-TG) complicated with HVOD were analyzed.</p><p><b>METHOD</b>All the drug related HVOD patients were treated with CCLG acute lymphoblastic leukemia (ALL)-2008 protocol. They were from Children's Hospital of Fudan University and Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from April 2008 to April 2009. The diagnosis was made according to the modified Seattle criteria and Baltimore criteria, including 2 or 3 of the following clinical features: hepatomegaly and upper right abdominal pain, jaundice (bilirubin ≥ 35 µmol/L), ascites or confirmed by pathology. The 6 HVOD patients' clinical manifestations, laboratory finding, imageologic and pathologic data were collected and analyzed.</p><p><b>RESULT</b>Of the 6 patients, 2 were males and 4 females. Mean age of the 6 patients was 3.89 years (range from 3 years 1 month to 4 years 11 months). The original disease was acute lymphoblastic leukemia. HVOD occurred during chemotherapy protocols of CAM (CTX + Ara-C + 6-TG) or maintenance period (MTX + 6-TG). Most of 6 HVOD patients presented with pain in liver area, hepatomegaly on imaging, elevated aminotransferase and bilirubin (often ≥ 35 µmol/L), hydroperitonia was common, one with pleural fluid, illegible hepatic veins. All the patients recovered after being treated with hepatoprotective, jaundice-relieving and supportive therapeutics, some patients were treated with low molecular weight heparin. The prognoses were good.</p><p><b>CONCLUSION</b>HVOD was a serious complication of chemotherapy with 6-TG. Hepatoprotective and jaundice-relieving and low molecular weight heparin could improve the prognosis.</p>