Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Objective:To investigate the effects of Yishen Decoction via colonic dialysis on intestinal flora and microinflammation in patients with chronic kidney disease (CKD) stages 3-5. Methods:A total of 156 patients with stage 3-5 CKD from the Second Affiliated Hospital of Guizhou University of Chinese medicine from October 2019 to October 2020 who met the inclusion criteria were divided into 2 groups of 78 patients according to the random number table method. The control group was given colonic dialysis treatment, the treatment group was given Yishen Decoction transcolonic dialysis treatment on the basis of the control group, and both groups were treated for 8 weeks. TCM syndrome scores were performed before and after treatment, serum levels of CRP, IL-6, and TNF-α were measured by ELISA, and SCR, BUN, and uric acid (UA) levels were detected by a fully automated biochemical analyzer. Fresh feces were collected from the patients, anaerobic culture and aerobic culture were performed, and the numbers of Bifidobacterium, Lactobacillus acidophilus, and Escherichia coli were counted to evaluate the clinical efficacy. Results:The total effective rate was 97.4% (76/78) in the treatment group and 84.6% (66/78) in the control group, and the difference was statistically significant ( χ2=7.847, P=0.005). At 4 and 8 weeks after treatment, the scores of lumbar and knee tenderness( t=6.596, 8.792), eating less and being dull ( t=12.060, 24.140) and pale complexion ( t=7.983, 12.300) in the treatment group were significantly lower than those in the control group ( P<0.01); the levels of bifidobacterium ( t=4.037, 2.358) and Lactobacillus acidophilus ( t=7.352, 2.092) were significantly higher than those in the control group, while the levels of Escherichia coli ( t=3.822, 6.084) were significantly lower than those in the control group ( P<0.01 or P<0.05). The serum CRP ( t=9.326, 12.300), IL-6 ( t=4.591, 4.716), TNF-α ( t=9.304, 9.775), SCr ( t=17.630, 11.530), BUN ( t=2.674, 2.248), UA ( t=10.860, 13.160) were significantly lower than those in the control group ( P<0.01 or P<0.05). Conclusion:Yishen Decoction can improve intestinal microecological status, inhibit microinflammatory response and relieve clinical symptoms for the patients with stage 3-5 CKD.

Objective:To understand the hereditary cancer related to germline TP53 mutations. Methods:A retrospective analysis was performed on a case of acute lymphoblastic leukemia(ALL) secondary to rhabdomyosarcoma admitted to Wuhan Children′s Hospital in February 2019.The clinical characteristics and gene detection were analyzed, and the correlative literature was studied.Results:The patient was diagnosed with rarely pleomorphic rhabdomyosarcoma at the age of 9 months, and only underwent complete excision without subsequent chemotherapy and radiotherapy.Seven years later, without exposure to suspicious carcinogenic risk factors, she was suffered from secondary ALL, germline TP53 mutations were confirmed by mutation gene detection and genetic verification.She received the induction treatment with Vincristine+ Daunorubicin+ L-Asparaginase+ Dexamethasone(VDLD), and then achieved the complete remission.According to the literature review result, there were 1 438 mutations emerging in TP53 gene, which were dominant by missense point mutations (707 kinds). These mutations could result in early-onset tumors that commonly arose in female patients.Molecular targeted therapy through TP53 gene mutation pathway could resist tumors. Conclusions:Germline TP53 mutation screening should be recommended for the early-onset tumor with genetic predisposition, and systematical monitoring of the family is also suggested, so as to early intervene and prevent the occurrence of the second tumor.The targeted drugs for germline TP53 mutations can reduce the toxicity of radiotherapy and chemotherapy and achieve high treatment effects.

Objective To investigate the correlation of serum calprotectin (MRP8/14) expression with clinical response in Chinese juvenile idiopathic arthritis (JIA) patients treated with a tumor necrosis factor (TNF) inhibitor.Methods Seventy-two JIA patients and 30 health volunteers (HCs) were enrolled in this prospective study.All JIA patients received etanercept for 24 weeks.Serum was collected from JIA patients at baseline before treatment and from HCs.Clinical response was defined according to the American College of Rheumatology (ACR) Pedi 50 criteria.Results Serum MRP8/14 expression was greater in JIA patients than in HCs (P ＜ 0.001).Serum MRP8/14 level was greater in responders than in non-responders (area under the receiver operating characteristic curve,0.823;95％ CI:0.706-0.939).Univariate and multivariate logistic analysis showed that high serum MRP8/14 expression was an independent predictive factor for clinical response (P =0.003).Conclusion Serum MRP8/14 level can be used as a convincing and novel biomarker for clinical response in JIA patients treated with a TNF inhibitor.

Objective To explore the observation and nursing of traumatic mediastinal hematoma.Methods The clinical data in 44 cases of mediastinal hematoma treated in our department from July 2006 to May 2016 were analyzed retrospectively.Results Forty cases were cured,4 cases(9％) died,the mortality rate was 9％,in which 1 case died from postoperative consumptive coagulopathy,1 case died from acute coronary syndrome and 2 cases died from traumatic hemorrhagic shock.Conclusion Timely diagnosis and treatment of intrathoracic cardiac and vascular injury are the key to save the lives of patients;the nursing focuses include observing the hematoma progress,adopting the comprehensive treatment measures such as controlled hypotension,limited fluid resuscitation and correctly selecting infusion approach for preventing hematoma enlargement and rupture.

OBJECTIVE:To investigate the characteristics and general rule of ADR induced by Ginkgo leaf extract and dipyri-damole injection,and to provide reference for clinical rational drug use. METHODS:UsingGinkgo leaf extract and dipyridamole injectionADRas subject,the journal articles were retrieved from CJFD during Jan. 1st,2005-Jun. 28th,2016,and then ana-lyzed statistically in respects of gender,age,primary disease,allergic disease,drug use,occurrence time of ADR,organs/systems involved and clinical manifestations. RESULTS:A total of 14 valid articles had been collected,involving 727 patients in total. Meanwhile,female was more than male(57.63% vs. 42.37%)and most of them aged more than 50 years;primary diseases were mainly thromboembolic disease and coronary heart disease;most of ADR happened within 30 min after medication (268 cases, 36.86%). Organs/systems involved in ADR were mainly nervous system (254 cases,28.60%),followed by skin and its appen-dants(228 cases,25.68%),digestive system(187 cases,21.06%);severe ADR could cause anaphylactic shock. There were 18 cases of new severe ADR (2.48%);all ADR cases were recovered,and no death occurred. CONCLUSIONS:It is suggested to strictly control indications,differential diagnosis and treatment,rational drug use,close monitoring through the whole process, maintain a high level of awareness to ADR.

Objective To investigate the utility of plasma procalcitonin (PCT) as an early predictor for postoperative complications in patients who underwent elective pancreaticoduodenectomy (PD).Methods Clinical data of 87 patients who underwent elective PD in Changhai Hospital from March.1, 2016 to Dec.31, 2016 were collected.The general data, postoperative recovery, serum PCT level and white blood cell (WBC) count before, 1 d, 3 d and 5 d after PD were recorded.ROC curve was drawn and AUC was calculated to determine the cutoff value, sensitivity and specificity.Patients were divided into complication group (n=42) and noncomplication group (n=45) based on the occurrence of post-operative complications, and the comparisons between the two groups were performed.Results There were no significant differences on the age, gender, diabetes, obstructive jaundice, laboratory tests including PCT, operative time, blood loss volume during surgery and tumor type between the two groups, which were comparable.Complication group had longer hospitalization than noncomplication group (24 d vs 15 d,P<0.001), and the differences were statistically significant.In complication group, 18 patients had pancreatic fistula, 13 had peritoneal infection, 7 had gastric empty dysfunction, 8 had bleeding, 2 had bile fistula and 2 had incision infection after PD.The postoperative plasma PCT level in patients with gastric empty dysfunction, bleeding, bile fistula and incision infection was not statistically different from those in noncomplication group (all P>0.05), but the plasma PCT level in patients with pancreatic fistula and peritoneal infection on 3 d and 5 d after PD was significantly higher than those in noncomplication group, and the difference was statistically significant (all P<0.05).The combination of plasma PCT and WBC on 3 d and 5 d after PD was superior to PCT or WBC alone in predicting pancreatic fistula (sensitivity 88.9%, 72.7%;specificity 68.5%, 78.2%) and abdominal infection (sensitivity 100%, 100%;specificity 45.9%, 44.4%).Conclusions Plasma PCT could predict the occurrence of abdominal infection and pancreatic fistula after PD.The combination of PCT and WBC might be more valuable in predicting abdominal infection and pancreatic fistula.

Objectives To detect gene mutation associated with hemophagocytic lymphohistiocytosis (HLH) and to identify mutation spectrum and clinical feature in HLH in children. Methods Thirty-seven (37) pediatric patients diagnosed with HLH according to 2004 clinical and laboratory criteria were enrolled from July 2012 to November 2015. Nucleotide sequences of all exons and their flanking intronic sequences of ten genes associated with HLH were amplified with PCR followed by direct sequencing. Point mutation analysis was performed after the direct sequencing. Results The median age of all the 37 patients was 2.6 years. The median ages of patients with gene mutation (n=22) and without gene mutation (n=15) was 2.09 years and 2.67 years, without statistical significance. Twenty-two patients were identified with gene mutations. All of them were heterozygous. UNC13D mutation (50%) is of the highest frequency in the above genes. The splicing mutations (38%) were the main type of UNC13D mutations,and missense mutations or frame-shift mutations were also found. There was no statistical difference in ages of onset and laboratory data of neutrophils, thrombocytes, NK cell activities within the three groups: multi-site mutations, single-site mutations and no mutations. EBV infection was detected in 70.3% patients. In mutation group, one patient died when he was in the period of inducing remission, and four patients were relapsed. Among them four patients were infected with EBV and one patients was negative at the onset while positive in recurrence. Conclusions UNC13D was the predominant causative gene in the Chinese population according our data. There was no significant relevance between age of onset, severity of disease and gene mutations. Attention should be paid to a patient with HLH gene mutation infected by EBV, which it might mean a poor prognosis.

Objective To investigate the mechanism by which heat shock protein 90 (HSP90) regulates 26S proteasome in hyperthermia. Methods Hyperthermic HepG2 cell models established by exposure of the cells to 42 ℃ for 3, 6, 12, and 24 h were examined for production of reactive oxygen species (ROS) and cell proliferation, and the changes in Hsp90α and 26S proteasome were analyzed. Results ROS production in the cells increased significantly after hyperthermia (F=28.958, P<0.001), and the cell proliferation was suppressed progressively as the heat exposure time extended (F=621.704, P<0.001). Hyperthermia up-regulated Hsp90α but decreased the expression level (F=164.174, P<0.001) and activity (F=133.043, P<0.001) of 26S proteasome. The cells transfected with a small interfering RNA targeting Hsp90α also showed significantly decreased expression of 26S proteasome (F=180.231, P<0.001). Conclusion The intracellular ROS production increases as the hyperthermia time extends. Heat stress and ROS together cause protein denature, leading to increased HSP90 consumption and further to HSP90 deficiency for maintaining 26S proteasome assembly and stability. The accumulation of denatured protein causes unfolded protein reaction in the cells to eventually result in cell death.