[Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma].

Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.

[Mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 regimen in the treatment of pediatric Burkitt lymphoma].

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ2=4.16, P=0.041) and group C2 (χ2=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ2=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.

Cerebral Digital Subtraction Angiography in Acute Intracranial Hemorrhage: Considerations in Critically Ill Children.

Cerebrovascular disorders are an important cause of morbidity and mortality in children. Although minimally invasive, cerebral digital subtraction angiography (DSA) has been shown to be safe in children and is a valuable, and perhaps underutilized, technique for the diagnosis and management of pediatric cerebrovascular disorders in the critical care setting. Through a case-based approach, we explore the utility of DSA in critically ill children with acute intracranial hemorrhage (ICH). We discuss the use of DSA in the acute management of aneurysm and arteriovenous malformation rupture as well as cerebral vasospasm. Those caring for critically ill children with acute ICH should consider cerebral DSA as part of a comprehensive approach to the diagnosis and management of these conditions.

[Multicenter clinical study on the diagnosis and treatment of childhood renal tumor].

Objective: To summarize the effect of Chinese Children's Cancer Group (CCCG) Wilms tumor (WT)-2015 protocol. Methods: This was a prospective study. CCCG-WT-2015 protocol was revised on the basis of the CCCG-WT-2009 protocol. Clinical data of 288 children diagnosed with newly diagnosed kidney neoplasms in fourteen pediatric centers between September 2015 to December 2018 were summarized. The age of onset, distribution of pathological subtypes, staging, curative effect and prognostic factors of these children were analyzed. Kaplan-Meier method was used for survival curve and Log-Rank method was used for univariate analysis. Results: Among 288 cases with kidney neoplasms, there were 261 cases of WT, including 254 cases (97.3%) with favorable histology (FH) WT and 7 cases (2.7%) with unfavorable histology WT (UFHWT). The 3 year events free survival (EFS) rate for FHWT and UFHWT were (88.9±2.1)% and (80.0±17.9)%, which were better than that in WT-2009 (81.2% and 71.7%). In the 96 cases of stage Ⅲ/Ⅳ FHWT with indications for radiotherapy, 76 cases received radiation, another 20 cases received M protocol chemotherapy (cyclophosphamide, etoposide, gentamycin, vincristine and adriamycin) instead of radiation. The 3 year EFS rate for these two groups were (84.7±4.3)% and (84.7±8.1)%(χ2=0.015, P=0.902). There were 22 renal clear cell sarcoma and 5 malignant rhabdoid tumor, 3 year EFS rate of them was (94.4±5.4)% and (20.0±17.9)%. Univariate analysis was performed for age, gender, pathological type, stage, whether rupture occurred during operation, whether complete remission (CR) occurred at the end of treatment and radiotherapy. Pathological types (χ2=44.329,P<0.01) and failure to achieve CR at the end of the treatment (χ2=49.459,P<0.01) were independent factor for predicting survival. Conclusion: Compared with CCCG-WT-2009, treatment of renal tumors in CCCG-WT-2015 study yielded good survival outcome, which can be further applied.

[Long-term results of multicenter study based on childhood acute lymphoblastic leukemia 2005 protocol].

Objective: To evaluate the long-term efficacy and prognostic factors of childhood acute lymphoblastic leukemia (ALL) enrolled in Shanghai Children's Medical Center-Acute Lymphoblastic Leukemia-2005(SCMC-ALL-2005) multicenter study. Methods: Between May 2005 and December 2014, 1 497 newly diagnosed ALL patients were enrolled and treated in 5 hospitals of SCMC-ALL-2005 study group, using risk-stratified SCMC-ALL-2005 protocol. Risk group classification and treatment intensity were based on clinical features, genetic abnormalities, early response to treatment and levels of minimal residual disease (MRD). Kaplan-Meier method was used to generate overall survival (OS) and event-free survival(EFS) curves. Cox proportional hazards models were used for multivariate analyses. Results: The patients were followed up to December 31, 2016, the median follow-up time was 69 months (24-141 months). The 5-year and 10-year OS rates were (80.0±1.0)% and (76.0±2.0)%. The 5-year and 10-year EFS rates were (69.0±1.0)% and (66.0±2.0)%. The 5-year and 10-year relapse rates were (23.0±1.0)% and (25.0±2.0)%. The 5-year OS and EFS for low risk (LR), intermediate risk (IR) and high risk (HR) were (91.1±1.4)% and (83.3±1.8)%, (79.2±1.5)% and (68.9±1.7)%, (52.9±4.4)% and (30.0±3.8)%, respectively. MRD negative status (<0.01%) on day 55 was seen in 792 patients (82.8%) and positive MRD on day 55 was associated with poor prognosis (OR=1.9, 95%CI: 1.3-2.7, P=0.001). Twenty-four HR patients received allogeneic hematopoietic stem cell transplantation and 17(70.8%) of them were alive and in remission. A total of 164 severe adverse events occurred, 46 of them died, treatment-related mortality was 3.1%. Conclusions: In this large sample research, the overall outcome for multi-center SCMC-ALL-2005 study was favorable. This helps to promote the standardized treatment of childhood ALL to the whole country. MRD results on day 55 of induction therapy have important prognostic and therapeutic implications.

Describing the quality of life of boys with haemophilia in China: Results of a multicentre study using the CHO-KLAT.

INTRODUCTION: The treatment of haemophilia varies across countries and across regions within some countries. Similar variation has been observed in health-related quality of life (HR-QoL). Relatively little is known about the HR-QoL of boys with haemophilia in China. AIM: The aim of this study was to describe the HR-QoL of boys with haemophilia in China using the Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT). METHODS: Boys (4-18 years of age) with haemophilia and their parents were enroled in a cross-sectional study. All parents/guardians of study subjects were requested to complete a CHO-KLAT questionnaire during a clinic visit, and report on several other clinical and socioeconomic factors in the past year. Boys who were > 7 years also completed the CHO-KLAT. RESULTS: A total of 269 parents of boys with haemophilia, from 13 hospitals in 12 provinces, were enroled during 2014. The boys ranged from 4.0 to 17.9 years of age; 91% had haemophilia A, most had moderate (52%) or severe (36%) disease, and most were receiving sub-optimal on-demand therapy or low-dose prophylactic therapy. Child self-report CHO-KLAT scores were available for 171 boys ≥7 years of age and ranged from 24.2 to 85.3 with a mean of 57.6 (n = 171). Parent proxy-reported CHO-KLAT scores ranged from 25.0 to 88.7 with a mean of 55.1 (n = 269). CONCLUSION: HR-QoL scores in boys with haemophilia in China were substantially lower than reported from Canadian and European boys with haemophilia. Longer term prospective studies are required to examine the factors impacting the HR-QoL for boys with haemophilia in China.

Liver injury induced by clomiphene citrate: A case report and literature reviews.

WHAT IS KNOWN AND OBJECTIVE: Clomiphene citrate is used to cause ovulation in females and to increase semen production in males. Clomiphene citrate is well tolerated in most patients and rarely induces liver injury. We report a case of liver injury which is associated with administration of clomiphene citrate in a male patient. CASE SUMMARY: A 31-year-old man who was treated by clomiphene citrate for 5 days was transferred to our emergency room with reddish-brown urine and upper abdominal pain. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were elevated. Based on the subsequent examination, he was diagnosed with liver injury and cholecystitis. The levels of AST and ALT returned to normal range after discontinuation of clomiphene citrate and symptomatic treatment. WHAT IS NEW AND CONCLUSION: The mechanism of liver injury caused by clomiphene citrate is still unclear. Polymorphism of CYP2D6 may have had an effect. Liver function tests should be performed when there is upper abdominal pain after administration of clomiphene citrate.

Analysis of meat flavor compounds in pedigree and two-strain Yangzhou geese.

In this study, we evaluated the meat flavor compounds of Yangzhou geese, including one group of pedigree strain (AA group) and 4 groups of 2-strain crossbreds (KA, KB, CA, and SA). Each group consisted of 100 geese comprised of 5 replicates of 10 males and 10 females each. Inosine 5'-monophosphate (IMP), amino acid (AA), and fatty acid (FA) levels in breast and thigh muscle were determined. Results showed that AA group had the highest levels of total amino acid (TAA) and dissolved free amino acids (DFAA) in breast muscle and of polyunsaturated fatty acids (PUFA) in thigh muscle (P<0.05). In SA group, the levels of C17:1, C22:0, C22:1, C20:4, and C24:1 in breast muscle were significantly higher in SA than in other groups (P<0.05). KB group had the lowest glycine levels in breast muscle (P<0.05) while MUFA levels were significantly higher in KB than in other groups (P<0.05). In KA, the levels of C18:3 in breast muscle in were higher than in CA and KB (P<0.05). CA had relevant higher IMPc levels in breast muscle than SA (P<0.05) and other groups (P>0.05); however, no significant differences were obtained in thigh muscle (P>0.05). In conclusion, Yangzhou AA goose has high levels of meat flavor compounds than its crossbreeds. Future efforts should focus on assessing meat flavor through measurement of sensory characteristics of Yangzhou geese.

The Effect and Mechanisms of Proliferative Inhibition of Crocin on Human Leukaemia Jurkat Cells.

Targeted therapy is a potentially useful approach for the treatment of T-lineage acute lymphoblastic leukaemia. This study aimed to find a highly effective, low toxic anti-tumour drug and further investigate its mechanisms. Jurkat cells were used as the object and were stimulated by different concentrations of crocin. By cell count, growth curve, MTT method for the detection of cell proliferation, annexin V/propidium iodide (PI) method for the apoptosis rates, and reverse transcription-polymerase chain reaction (RT-PCR) for bcl-2 and bax gene expression, the effect and mechanisms of proliferative inhibition of crocin on Jurkat cells were further explored. Crocin promoted Jurkat cell apoptosis and inhibited cell growth, in a dose-time-dependent manner. The mechanism might be related to the inhibition of bcl-2 gene expression and the promotion of bax gene expression. These results suggest that crocin can be used as a suitable clinical agent for the treatment of T-lineage acute lymphoblastic leukaemia.

Crocin attenuates cisplatin-induced liver injury in the mice.

Cisplatin (CDDP) is one of the most frequently used antitumor agents, but its application is significantly limited by its hepatotoxicity. In the present study, we investigated the effects of crocin against CDDP-induced oxidative stress and apoptosis in the liver of Kunming mice. Crocin was administered to the mice once daily for 7 consecutive days at the doses of 6.25 and 12.5 mg/kg body weight orally. On day 1, a single intraperitoneal injection of CDDP was given at the dose of 10 mg/kg body weight. Crocin treatment significantly improved CDDP-induced hepatic damage as indicated by serum aspartate aminotransferase and alanine aminotransferase levels. Crocin relieved CDDP-induced oxidative stress by reducing malondialdehyde level and recovering the levels of glutathione and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. In addition, liver histopathology indicated that crocin alleviated CDDP-induced focal necrosis. Immunohistochemical staining and Western blot analysis showed that crocin significantly decreased the levels of phospho-p38 mitogen-activated protein kinase (MAPK), tumor protein 53 (p53), and cleaved caspase-3. Taken together, our data suggest that crocin provides protective effects against CDDP-induced hepatoxicity by attenuating oxidative stress and inhibiting the activation of p38 MAPK, p53, and caspase-3.

Stereoselective metabolism of silybin diastereoisomers in the glucuronidation process.

A separation method for the hepatoprotective drug silybin and its metabolites by RP-HPLC was described. Based on this separation, the stereoselectivity of the metabolism of silybin was investigated by incubation of the drug and its two diastereoisomers with bovine liver microsomes. Information about the structures of these metabolites was obtained, using UV, HPLC/MS and NMR spectra. Four major metabolites (M(1), M(4) of silybin A and M(2), M(5) of silybin B), were prepared by preparative HPLC, and their configurations were accomplished by NMR spectra. A HPLC method was used to quantify the metabolites. The results showed that silybin was extensively metabolized and the major sites for glucuronidation were the C-20, C-7, at phenolic OH groups. Furthermore, the results obtained reveal that there was significant stereoselectivity in the glucuronidation process of silybin. Silybin B was glucuronidated at a more efficient rate than its diastereoisomer, and glucuronidation of silybin B was much preferred at the 20 position, while that of silybin A was similar at both 7 and 20 position.

Extracellular inhibition and intracellular enhancement of Ca2+ currents by Pb2+ in bovine adrenal chromaffin cells.

1. Effects of highly neurotoxic, inorganic lead ions (Pb2+) on voltage-dependent calcium channels were investigated with the use of the whole cell patch-clamp technique in bovine adrenal chromaffin cells maintained in short-term primary culture (1-5 days). 2. Extracellularly applied Pb2+ induced a concentration-dependent, reversible inhibition of Ca2+ currents, with an estimated IC50 approximately equal to 3.0 x 10(-7) M free Pb2+. 3. Elevation of the intracellular free Ca2+ concentration above 10(-8) M dose-dependently reduced the amplitude of the initial Ca2+ current and increased the exponential rate of current rundown. 4. Intracellularly applied Pb2+ prevented the Ca(2+)-dependent reduction of the initial Ca2+ current amplitude and altered the current rundown kinetics from exponential to linear. The effect was dose dependent and saturable, with an estimated EC50 approximately equal to 2.0 x 10(-10) M free Pb2+. 5. These results indicate that in contrast to extracellular blockade, intracellular Pb2+ promotes Ca2+ currents by attenuating the Ca(2+)-dependent, steady-state inactivation of calcium channels. This provides a novel mechanism through which Pb2+ may disrupt calcium signaling in chronically lead-exposed cells.

Pb2+ activates potassium currents in bovine adrenal chromaffin cells.

Inorganic lead (Pb2+) is a potent environmental toxin which adversely affects several aspects of neuronal and secretory cell function. In this report, we provide evidence that at subnanomolar concentrations, Pb2+ activates the outward K+ currents in bovine adrenal chromaffin cells. Whole-cell patch clamp combined with intracellular perfusion was employed to monitor outward K+ currents in bovine chromaffin cells before and after intracellular application of EGTA-Pb buffers. Intracellular Pb2+ > or = 10(-10) M enhanced the K(+)-currents in a concentration dependent manner, with apparent K0.5 approximately equal to 5 x 10(-10) M. Extracellular application of 40 nM Charybdotoxin (ChTX) blocked the Pb(2+)-dependent component of outward currents, suggesting that Pb2+ activates the large conductance Ca(2+)-dependent K+ channels.