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.

Objective:To evaluate the subjective feeling and the objective chewing effect of the patients with the prosthesis made for upper jaw defect by altered cast impression technique.Methods:A self-control experiment was conducted for 30 patients with the pros-thesis made for upper jaw defect by specific tray impression technique and altered cast impression technique respectively.As soon as the impression was finished,the patients were required to finish 2 questionnaires,one was about their self-comfortable sensation and the other one was the STAI(State-Trait Anxiety Inventory)about their feeling of anxiety.Then the chewing-effect was tested.Data were analysed by SPSS 20.0 software (T-test and Rank-sum test).Results:Most prosthesis made by altered cast impression technique showed increased masticatory function(P <0.05).The subjective-felling evaluation indicated that the altered cast impression technique was more comfortable but there was no difference between the 2 methods in the whole course of the impression(P =0.051).STAI score showed that the patients suffered lower anxiety with altered cast impression.Conclusion:The altered cast impression technique can en-hance masticatory efficiency and increase the satisfaction of patients for preparation of the posthesis for upper jaw defect.

OBJECTIVE:To observe clinical efficacy and safety of tanshinone combined with limbal stem cells transplantation in the treatment of pterygium. METHODS:Totally 97 cases (118 eyes) of primary pterygium admitted into our hospital during Feb. 2010-Sept. 2014 were analyzed retrospectively,and divided into observation group (48 cases,57 eyes) and control group (49 cases,61 eyes). Both groups received autologous limbal stem cell transplantation. The control began to give Tobramycin and dexamethasone eye drops 1-2 drop 1 week before surgery,every 4-6 h one times. Observation group was given Tanshinone cap-sules 0.5 g,po,tid,one week before surgery,for 3 months. Repair time of corneal epithelium and local symptom regression time were compared between 2 groups. Corneal astigmatism and corrected visual acuity were observed in 2 groups before and 1,3 months after surgery. The occurrence of recurrence and ADR was analyzed statistically in 2 groups. RESULTS:The repairing time of corneal pithelial and local symptom regression time in observation group were significantly shorter than control group,with statis-tical significance (P<0.05). There was no statistical significance in corneal astigmatism and corrected visual acuity between 2 groups before and one month after surgery (P>0.05). 1,3 months after surgery,corneal astigmatism of 2 groups was decreased significantly and corrected visual acuity was increased significantly than before surgery,and 3 months after surgery the observation group was significantly better than the control group,with statistical significance (P<0.05). The recurrence rate of observation group was 3.51%,which was significantly lower than 14.75% of control group,with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Tanshinone combined with autol-ogous limbal stem cell transplantation in the treatment of pterygium can shorten the time of corneal epithelial repair and local symp-toms,restore the visual function of patients and reduce recurrence rate with good safety.

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 To investigate the dynamic expression and significance of B cell lymphoma (Bcl) 6 in fibroblast-like synoviocytes (FLS) induced osteoclast differentiation and activation in rheumatoid arthritis (RA) patients.Methods RA-FLS were co-cultured with peripheral blood monocytes (PBMCs) from healthy volunteers in the medium containing M-CSF.Bcl6 protein and mRNA in osteoclasts and their precursors were determined by immunofluorescence and Real-time PCR at day 0,7,14 and 21,respectively.Osteoclasts were identified by tartrate-resistant acid phosphatase (TRAP) staining.Bone resorption activity of osteoclasts was determined by bone slices stained with toluidine blue.Kruskal-Wallis H and Bonferroni were used for statistical analysis.Results ① Immunofluorescence staining and TRAP staining showed that Bcl6 protein was mainly expressed in the nuclei of PBMCs.After co-cultured with RA-FLS for 7 days,some PBMCs differentiated into macrophages and a few differentiated to TRAP-positive multinucleated osteoclasts,and the total Bcl6 protein expression in osteoclasts and their precursors were increased.At day 14,the total Bcl6 protein expression was increased further.At day 21,the Bcl6 protein expression in nuclei of osteoclasts was decreased while PBMCs were differentiated into osteoclasts,and total Bcl6 protein expression was decreased.②Real-time PCR showed that Bcl6 mRNA expression in osteoclasts and their precursors at day 7 tended to increase than that at day 0 (x2=3.429,P＞0.05).At day 14 after co-cultured with RA-FLS,Bcl6 mRNA expression in osteoclasts and their precursors was significantly higher than that at day 0 (x2=5.333,P=0.045).At day 21,the expression of Bcl6 mRNA was significantly lower than that at day 14 (x2=6.023,P=0.038).Conclusion Bcl6 may be involved in osteoclast differentiation and activation,and may play a role in the inflammatory status in the process of differentiation from PBMCs to macrophages.Further studies are needed to establish the mechanisms.

Objective To investigate the predictive value of peripheral blood neutrophil to lymphocyte ratio (NLR) for early stroke risk after transient ischemic attack (TIA).Methods Patients with TIA admitted to the Department of Neurology,the Second Hospital of Tianjin Medical University from August 2015 to July 2017 were enrolled retrospectively.According to whether or not ischemic stroke occurred within 90 d after the onset of TIA,they were divided into stroke group and non-stroke group.Multivariate logistic regression analysis was used to determine the independent risk factors for early stroke after TIA,and the receiver operating characteristic curve was used to evaluate the predictive value of baseline NLR for early stroke risk after TIA.Results A total of 131 patients with TIA were enrolled.Among them,23 (17.5％) had a stroke within 90 d,mainly within 7 d after the onset of TIA (n =13,56.5％).Univariate analysis showed that the differences between the two groups were statistically significant in terms of age,ABCD2 score,hypertension,duration of symptoms ≥60 min,diabetes,triglyceride,baseline NLR level,intracranial artery stenosis,use of antiplatelet drugs and dual antiplatelet drugs (all P ＜ 0.05).Multivariate logistic regression analysis showed that after adjusting for the confounding factors,the baseline NLR level (odds ratio [OR]2.631,95％ confidence interval [CI] 1.372-5.046;P =0.004) and ABCD2 score (OR 3.049,95％ CI 1.130-8.226;P =0.028) were the independent risk factors for early stroke after TIA,and use of dual antiplatelet agents (OR 0.195,95％ CI 0.046-0.826;P =0.026) were the independent protective factor.The receiver operating characteristic curve analysis showed that when the NLR cut-off value was 2.84,the area under the curve was 0.803 (95％ CI 0.716-0.889),and the sensitivity and specificity of predicting early stroke risk after TIA were 80.8％ and 69.5％,respectively.Conclusion Higher baseline NLR has certain predictive value for early stroke risk after TIA.

Objective To investigate the predictive value of early neutrophil to lymphocyte ratio(NLR) in peripheral blood for long-term recurrence of ischemic stroke. Methods Patients w ith first-ever acute ischemic stroke w ere enrolled prospectively. The demographics and baseline clinical data of the patients at admission w ere documented and NLR w as calculated. According to the results of 2-year follow-up, they w ere divided into the recurrence group and the non-recurrence group. Multivariate Cox regression analysis w as used to identify the independent risk factors for stroke recurrence and receiver operator characteristic (ROC) curve w as used to evaluate the predictive value of baseline NLR level for recurrent risk of ischemic stroke. Results A total of 395 patients w ith acute ischemic stroke w ere enrolled, 76 patients had recurrence (19.2%) during the follow-up period. Univariate analysis show ed that there w ere significant differences in age,smoking,hyperlipidemia, atrial fibrillation, baseline National Institutes of Health Stroke Scale (NIHSS) score, total cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, homocysteine, NLR, and discontinuation of statins betw een the recurrence group and the non-recurrence group (all P<0.05). Multivariate Cox regression analysis show ed that the baseline NLR level w as an independent risk factor for the recurrence of ischemic stroke (hazard ratio 1.087,95% confidence interval 1.025-1.363; P=0.021). ROC curve analysis show ed that w hen the baseline NLR cutoff value w as 3.61,the area under ROC curve w as 0.756 (95%confidence interval 0.692-0.821).The sensitivity and specificity of predicting recurrence in patients w ith ischemic stroke w ere 73.7% and 73.0%, respectively. Conclusion The higher baseline NLR has a certain predictive value for recurrence of ischemic stroke.

Venous thromboembolism (VTE) is one of the most serious complications of cancer, which has become the second leading cause of death in cancer patients. Therefore, early prediction and prevention of VTE plays an important role in improving the prognosis of cancer patients.In recent years, with the continuous development of experimental techniques and clinical medicine, the laboratory should pay attention to assist in clinical prediction of tumor thrombosis risk, and understand the predictive model of tumor thrombosis risk, the new progress of predictive indicators and their clinical application potential.

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.

Clinical biochemical examination is an important part of medical laboratory, and it is also the key and difficult point of all kinds of examinations.However,the teaching of clinical biochemistry is easily to enter the misunderstanding of "focusing only on the instrument operation, while others depend on self-study". There is even confusion that teachers don′t know what to teach and students don′t know what to learn.In this paper, the teaching experience of the clinical biochemical laboratory is described,formulated a scientific block training program, adopted the teaching mode of combining tutorial responsibility with daily teaching,flexibly used a variety of teaching methods and procedural examinations, and greatly improved the teaching quality.