In recent years, the incidence of pediatric malignancies has gradually increased. High-risk patients have poor prognosis, and the main effect of treatments such as surgery and radio-chemotherapy has reached a plateau phase. Targeted therapy, with its reliable efficacy and mild toxicity, has become one of the most promising approaches. Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase, and its abnormal forms include gene fusion, gene mutation, gene amplification, and protein overexpression. These aberrations play important roles in the development of childhood cancer. With the application of ALK inhibitors in clinical anti-tumor therapy, targeted ALK treatment has received increased attention. This article aims to review various studies on the relationship between ALK aberrations and pediatric malignancies.

ObjectiveTo explore the changes of the levels of cytokines in patients with first-episode depression and the effect on the levels of cytokines after the treatment with duloxetine.MethodsThe serum levels of interleukin 1 ( IL-1 ),interleukin 6 ( IL-6 ),tumor necrosis factor-alpha ( TNF-αt ),interleukin4 ( IL-4 ),interleukin10(IL-10) were measured in 38 patients with depression before and after duloxetine treatment by enzyme linked immunosorbent assay(ELISA).HAMD score were assessed at pre- treatment and post-treatment to assess curative effect.The control group was 30 healthy individuals.All data were statisticaly analyzed by SPSS.ResultsBefore treatment,the HAMD score and the levels of serum IL-6,TNF-α,IL-1 in first-episode depressant patients were remarkablely higher than those in the control group( IL-6:( 10.66 ± 3.12 ) pg/ml vs (2.72 ± 0.91 ) pg/ml ;TNF-α:(77.49 ±3.12) pg/ml vs (37.48 ±5.87) pg/ml; IL-1:(39.09 ± 3.77 ) pg/ml vs ( 10.31 ± 1.05 ) pg/ml ),the levels of serum IL-4 and IL-10 in first-episode depressant patients were remarkablely lower than those in the control group(P＜0.05,P＜0.01 ).The HAMD score and the levels of serum IL-6,TNF-α,IL-1 in post-treatment were remarkablely lower than pre-treatment (P ＜ 0.05 ),but which were still higher than the control group(P＜ 0.05 ).The levels of serum IL-4 and IL-10 in post-treatment were remarkablely increased than pre-treatment(P＜0.05).The levels of serum IL-6,TNF-α,IL-1 were positively correlated with the HAMD score( r =0.667,0.486,0.727,P ＜0.01 ),but the levels of serum IL-4 and IL-10 were negatively correlated with the HAMD scorae ( r=-0.433,-0.269,P＜0.05,P＜ 0.01 ).ConclusionsThe first-episode depressant patients show immune disorder induced by cytokines.Anti-depressant activity of duloxetine may participate in the regulation of cytokines and Th1/Th2 unbalance.

ABSTRACT:Objective To explore the effects of miRNA-1246 (miR-1246)on cell proliferation,invasion and migration in human cervical squamous cell carcinoma (CSCC)cell line SiHa.Methods SiHa cells were assigned into 3 groups:miR-1246 analog group,miR-1246 antagonist group and control group.Transfection efficiency was determined.The MTT assay,transwell assay and wound healing assay were performed respectively to evaluate the proliferation,invasion and migration abilities of SiHa cells.Western blot was carried out to detect the expression of thrombospondin-2 (THBS2)before and after transfection.A THBS2 3’-UTR-containing dual luciferase plasmid was synthesized and co-transfected with miR-1246 into SiHa cells to observe the luciferase enzyme activity.Results MTT assay,transwell assay and wound healing assay revealed that the abilities of proliferation,migration and invasion were significantly enhanced (P<0.01)in SiHa cells transfected with miR-1246 analog,but suppressed in SiHa cells transfected with miR-1246 antagonist.Western blot showed that SiHa cells transfected with miR-1246 analog had significantly decreased THBS2 expression (gray value = 6 .2 8 ± 1 0 .2 2 , P=0 .0 1 3 ) while those transfected with miR-1246 antagonist had significantly increased THBS2 expression (gray value = 12.90±19.81, P=0.037).After co-transfected with miR-1246 and THBS2 3’-UTR-containing plasmid,SiHa cells exhibited a decreased level of luciferase enzyme expression.Conclusion miR-1246 promoted the proliferation,invasion and migration of CSCC SiHa cell, and it might promote CSCC tumorigenesis and progression by suppressing the expression of its target gene THBS2 .

Objective To evaluate the clinical outcome of NB09 (China Pediatric Neuroblastoma cooperative group 09) protocol on children with high-risk and ultra-high risk neuroblastoma. Methods The clinical and follow-up data of pa?tients who suffered from high-risk (n=7) and ultra-high risk (n=31) neuroblastomas and admitted in Tumor hospital of Tian?jin Medical University between January 2009 to January 2013 were retrospectively reviewed (27 boys and 11 girls). The age at diagnosis was 19-160 months (median age was 36.5 months). In the high risk group, patients were evaluated and operated after 4 to 6 circles of neoadjuvant chemotherapy. In ultra-high risk group, patient received chemotherapy before and after op?eration, then autologous stem cell transplantation and tumor bed radiotherapy. After chemotherapy, retinoic acid treatment was given to patients in ultra high risk group as in high risk group. Results At the end of treatment, 25 patients achieved complete remission; 5 patients achieved partial remission; 3 patients were in stable disease;5 patients were deteriorating in their conditions which lead to 2 deaths. In total, the response rate reaches upto 86.8%. By the end of follow up, 15 patients had a disease-free-survival, 9 patients survived with tumor, 7 died from recurrence and 7 died from deteriorating conditions. Survival time ranged from 6 to 52 months (median survival 25.5 months). The 1-, 2- and 3-year overall survival were 91.7%, 64.5%and 57.3%respectively. Kaplan-Meier curve and Log-rank test showed no statistical significance between high risk and ultra-high risk neuroblastomas. Conclusion The outcome of NB09 protocol for high risk and ultra-high risk neuroblastoma was preliminary affirmed. It is worthy of further clinical verification.

Objective According to analyse SCI papers published by hospital faculties during the period of 2010-2015,this paper discussed influential factors and strategies for paper publishing from the perspective of hospital scientific research management,proposed suggestions to administrative department and leaderships for decision making.Methods Taking SCI database developed by Institute for Scientific Information (ISI) as data resource.Literature analysis method was used to analyze the SCI papers during 2010 2015 in terms of publishing amount,subject development,periodical distribution,foundation support,citation analysis,etc.Results The amount of the SCI papers increased sharply each year with a wide spread of extensive subjects which reveals the development of the medical research.However,the average Impact Factor of the paper is still struggling behind that of the top medical institutes.Most papers published in the hospital is supported by National Science Foundation of China (NSFC).Conclusions This paper proposed that the hospital needs to establish a series of policies to strengthen the project management and talent training in the long run,encourage publishing high quality papers to promote the development of disciplines,increasing the investment for constructing research platforms and also making good use of administration for better research.

Objective:To investigate the etiology, clinical characteristics, and treatment of myelodysplastic syndrome/acute my-eloid leukemia (t-MDS/AML) secondary to malignant tumors. Methods: We retrospectively analyzed 11 patients with t-MDS/AML and investigated the treatment of primary tumors, clinical manifestations, treatment, and survival of t-MDS/AML patients. Results:A total of 11 patients were exposed to cytotoxic chemotherapeutic agents or radiation therapy for their primary tumors. The median laten-cy was 36 months. Common symptoms were fatigue, dyspnea, bleeding, and infection, all of which were related to deficits in hemato-poiesis. Therapeutic regimen included support therapy, immunomodulatory therapy, and chemotherapy. The median overall survival and disease-free survival periods were 28 months and 19 months, respectively, and the overall survival rate for 3 years was 44.4%. Conclu-sion:t-MDS/AML is a serious complication of chemotherapy or radiotherapy for a malignant or nonmalignant condition. The curative effect is limited, and prognosis is poor. Therefore, we should take t-MDS/AML into consideration when making treatment plans for can-cer patients to evaluate treatment benefits and to avoid treatment-related complications.

Objective:To investigate the value of ultrasound combined with thyroglobulin (Tg) in preoperative N staging of thyroid carcinoma.Methods:The clinical data of 1 138 patients with thyroid carcinoma in the Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) from August 2018 to October 2020, who confirmed by surgery and pathology were analyzed retrospectively. The 1 138 cases were divided into pN0, pN1a, and pN1b stages. Kappa consistency test was used to analyze the consistency of ultrasound evaluation of N staging and pathological N staging. Pathology result was taken as the gold standard to analyze the correlation between some preoperative serum markers and lymph node metastasis. The ROC curve was used to compare the diagnostic value of ultrasound, Tg, and ultrasound combined with Tg for lymph node metastasis.Results:The preoperative ultrasound assessment of N staging was moderately consistent with pathology(Kappa=0.459, P<0.01). Between pN0 and pN1(pN1a+ pN1b) stages, the differences in free triiodothyronine (fT3), anti-thyroid peroxidase antibody (TPOAb) and Tg were statistically significant (all P<0.05). Among the different indicators, only Tg had significant effect on lymph node metastasis ( P<0.01) .The area under the ROC curve (AUC) of Tg in predicting lymph node metastasis of thyroid cancer was 0.679, while the best cut-off value for Tg was 25.245 μg/L. The AUC of only ultrasound and ultrasound combined with Tg were 0.699 and 0.775, respectively. Therefore, combined diagnosis method was better than ultrasound only. Conclusions:Preoperative ultrasound and thyroglobulin has a specific value in evaluating the N staging of thyroid carcinoma. The combination of the two is more valuable in the diagnosis of lymph node metastasis than ultrasound only.

Objective To summarize the pathology of congenital intestinal atresia,the incidence and prenatal diagnosis rate of different types,and to analyze the location and type of intestinal atresia as well as the factors that affect the mortality of various types of intestinal atresia.Method We retrospectively analyzed the clinical data of 147 children with congenital intestinal atresia from January 2013 to March 2016,including gender,gestational age,parity,prenatal diagnosis or not,delivery methods,hospital admission,surgical methods,findings during surgery,combined malformations,complications and prognosis.They were analyzed statistically.Result A total of 147 cases,including 69 males and 78 females were enrolled.There were 40 premature infants and 107 full term cases.Twins were found in 3 cases.Hospital admission age range from 1 hour to 62 days;admission weight range from 1 480 g to 4 200 g;32 cases were diagnosed before birth.2 cases were abandoned before surgery because of trisomy 21.Postoperatively,the occlusion sites was confirmed as following:67 cases (46.2％) in ileum,43 cases (29.7％) in jejunum,26 cases (17.9％) in duodenum,and 9 cases (6.2％) in colon.The pathological types were as following:type Ⅰ 42 cases (29.0％),type Ⅱ 8 cases (5.5％),type Ⅲa 65 cases (44.8％),type Ⅲb 15 cases (10.3％) and type Ⅳ 15 cases (10.3％).22 cases (14.9％) were died because of refusal of treatment:7 cases were due to short bowel syndrome and meconium peritonitis,6 cases were due to postoperative chronic pseudo-obstruction,and 5 cases had anastomotic leakage requiring reoperation.1 case had postoperative enterocolitis and gave up treatment,1 case had anastomotic leak and sever systemic post-surgery infection and gave up further treatment,and 2 cases gave up because of 21-trisomy syndrome.Conclusion The operation plan of intestinal atresia should be based on the location and type of the blockade;the location and complications of the blockade (pseudo-obstruction,short bowel syndrome,and anastomotic leakage) are important factors affecting the treatment and prognosis.

Objective To investigate the effect of surgical treatment of necrotizing enterocolitis (NEC) with different surgical ages.Methods From January 2014 to December 2017,105 neonates with NEC in our hospital were divided into early operation group (operation age ＜ 7 days,n =47) and late operation group (7 ＜ operation age ＜ 28 days,n =58).The general data,surgical indications,intraoperative conditions,surgical methods,postoperative complications,and postoperative survival rates were compared between the two groups.Results Among the 105 neonates with NEC,74 were male and 31 were female.The average birth weight was (2 398 ± 927)g,and the average gestational age was (35 ± 4)weeks.Compared with the early operation group,the late operation group had lighter birth weight,smaller gestational age and higher rate of respiratory failure (P ＜ 0.05).There was no significant difference between the two groups in the proportion of surgical indications (diffuse peritonitis,pneumoperitoneum,and medical treatment ineffective) (P ＞ 0.05).The necrosis rate of small intestine in the late operation group was higher than that in the early operation group,but the necrosis rate of small intestine and colon was lower than that in the early operation group (P ＜ 0.05).There was no significant difference in the proportions of the two groups in the surgical methods (enterostomy,intestinal resection and anastomosis and enterostom,exploratory laparotomy,abdominal drainage,and intestinal resection and anastomosis) (P ＞ 0.05).The incidence of intestinal stenosis in early operation group was higher than that in late operation group (P ＜ 0.05).The survival rate of early operation group was 78.7％,while that of late operation group was 63.8％,with no significant difference (P ＞ 0.05).Conclusions The patients with NEC who were operated within 1 week after birth are more common in term infants and with colon necrosis,and are more likely to occur intestinal stenosis after surgery.The patients with NEC who were operated after 1 week of birth are more common in prematures and low-birth-weight patients,and are often associated with respiratory failure.Pneumoperitoneum and diffuse peritonitis are common surgical indications for NEC.Enterostomy is the major surgical method.Choosing the right timing and surgical method can improve the prognosis of patients with NEC.

Objective In this study, we aimed to detect the level of total circulating microparticles (MPs) in pregnant women with preeclampsia (PE) and analyze the proteome of MPs to explore their roles in the pathogenesis and progression of PE. Methods 98 pregnant women with PE, 54 healthy pregnant women, and 51 healthy non-pregnant women were enrolled from December 2016 to June 2018, whose MP levels were detected by flow cytometry and compared. Proteins extracted from the MPs were analyzed by high performance liquid chromatography mass spectrometry.Results The total MP level of the healthy pregnant group was significantly higher than thatof the non-pregnant group [159.87 (113.25, 218.18)/μl vs 94.10 (53.35, 140.23)/μl, P=0.004], but was not significantly different from that of the PE group. By proteomic profiling, 30 differential proteins were obtained between healthy pregnant women and healthy non-pregnant women, which were closely related to biological processes such as complements, coagulation cascades, angiogenesis and so on; 14 differential proteins were found between PE patients and healthy pregnant women, which were closely related to biological processes such as coagulation cascades, complements and inflammatory reactions, angiogenesis and so forth. Conclusions The level of circulating MPs may reflect the hypercoagulability of preeclampsia. In addition, circulating MPs may be involved in the pathogenesis of PE through various pathways by carrying different proteins, which indicates their potential value in the intervention of PE.