Pediatric cancer is one of the leading causes of death in children around the world.Although radiotherapy is an important means of treatment for pediatric cancer,it causes acute or chronic adverse events that may affect patients' survival time and quality of life.As a novel and advanced radiation technique,proton therapy allows for precise dose delivery in target volume,significantly reducing the irradiation to surrounding tissues and organs.Studies have shown that proton therapy is well tolerated in the treatment of pediatric cancer,and it achieves good tumor control;proton therapy is superior to traditional radiotherapy in improving quality of life,protecting intelligence,and reducing the risk of secondary cancer.This article reviews the research advances in the application of proton therapy in the treatment of pediatric cancer.

Objective To study the effect of 17α-hydroxyprogesterone caproate (17P) and medroxyprogesterone acetate (MPA) on expression of tumor necrosis factor-α (TNF-α)and cyclooxygenase-2 (COX-2) in placenta and uterine myometrium of inflammation-induced preterm birth mouse model to investigate the mechanism of preventing inflammation-induced preterm birth by progestogen.Methods Thirty clean CD-1 mice were divided into 6 groups (5 mice in each group) at 15th day of gestation:control group,lipopolysaccharides (LPS) group,17P 1 mg+LPS group,17P 2 mg+ LPS group,MPA 1 mg+LPS group and dimethyl sulfoxide (DMSO) + LPS group.Progestogens at different dosage were administered 1 h before LPS and 6 h after LPS administration.After these mice were sacrificed,TNF-α and COX-2 levels in the myometrium and placenta were detected by real-time PCR and immunohistochemistry.Data were analyzed by ANOVA,and comparisons between groups were adopted LSD method.Results 1.The comparison of relative expression of COX-2 mRNA and TNF-α mRNA in myometrium and placenta among groups:(1) Expressions of COX-2 mRNA and TNF-α mRNA in myometrium and placenta in the study groups were obviously higher than those of control group (P＜0.05).(2) COX-2 mRNA expression in myometrium of 17P 1 mg+LPS group (11.410±3.931),17P 2 mg+LPS group (8.352±3.209) and MPA 1 mg+LPS group (11.920± 2.905) were obviously lower than that of LPS group (20.540± 4.147) and DMSO+ LPS group (18.620 ± 4.156) (P＜0.05,respectively) ; although TNF-α mRNAexpression had similar trends among these groups,there were no statistical significance (P＞0.05,respectively).(3) COX-2 mRNA expression in placenta of 17P 1 mg+LPS group (10.864±3.777),17P 2 mg+LPS group (7.084±1.667) and MPA 1 mg+LPS group (11.830±3.652) were obviously lower than that of LPS group (18.920±4.106) and DMSO+LPS group (23.820±7.554)(P＜0.05,respectively).(4) TNF-α mRNA expression in placenta in 17P 1 mg+LPS group (14.340±1.618),17P 2 mg+ LPS group (11.488 ± 2.910) and MPA 1 mg+ LPS group (13.040 ± 2.982) were obviously lower than that of LPS group (24.240±7.059) and DMSO+LPS group (23.040±5.896) (P＜0.05,respectively).2.The comparison of protein expression of COX-2 and TNF-α in placenta among groups:(1) The expression of COX-2 protein in placenta of the study groups was significantly higher than that of control group (P＜0.05).(2) There were no differences among the COX-2 protein expression of 17P 1 mg+ LPS group (14 360.92± 1766.01),17P 2 mg+ LPS group (13 340.18±965.35) and MPA 1 mg+LPS group (12 870.81±1521.97)(P＞0.05),while the COX-2 protein expressions of them were significantly lower than that of LPS group (16 426.64 ± 1823.87) and DMSO+LPS group (16 761.23±2388.17)(P＜0.05,respectively).(3) There were no differences among the TNF-α protein expression of 17P 1 mg+LPS group (22 750.96±4656.68),17P 2 mg+LPS group (22766.24± 3500.34) and MPA 1 mg+LPS group (20770.01±3318.48)(P＞0.05),while the TNF-α protein expressions of them were significantly lower than that of LPS group (26204.49±5090.34) and DMSO+LPS group (27346.18±3269.30)(P＜0.05,respectively).Conclusions 17P and MPA might prevent the preterm parturition of inflammation-induced mouse model by inhibiting inflammation cytokines and prostaglandins.

Objective:To investigate the status of vitamin D deficiency in middle aged and elderly patients at an orthopedic department.Methods:The data of 25-hydroxy vitamin D[25(OH)D]in patients aged over 55 years at an orthopedic department in Beijing Hospital from November 2014 to January 2020 were collected.The differences in serum 25(OH)D status were compared in different gender and age.Results:A total of 3004 subjects were included with 725 males and 2279 females, ranged from 55 to 102 years old with an average of(71.1±9.7)years.The average serum 25(OH)D level was(17.77±9.92)ng/ml, which was diagnosed as vitamin D deficiency status.Serum 25(OH)D levels were(19.66±9.77)μg/L, (18.34±9.78)μg/L, (16.19±9.51)μg/L and (14.74±10.49)μg/L, at different age groups of 55-64, 65-74, 75-84, 85 years and over, respectively, with statistically significant differences( F=29.357, P<0.05). Serum(OH)D levels of patients were severely deficient, deficient, insufficient and sufficient, with their proportion of 21.3%, 44.6%, 23.3% and 10.8%, respectively.The proportion of patients achieving from vitamin D levels severe deficiency to deficiency to insufficient to sufficient were 18.2%, 44.8%, 25.1% and 11.9% in men, and 22.2%, 44.6%, 22.7% and 10.5% in women, respectively. Conclusions:The deficiency of vitamin D is prevalent in elderly patients visiting at orthopedic department.Serum 25-hydroxy vitamin D has a decreased trend along with age increasing, showing an increased trend of vitamin D deficiency.Patients with severe vitamin D deficiency are the focus for the intervention.

Objective To study 3D construction and printing of bone tissue engineering scaffolds by bone defect modeling on Mimics software based on CT data. Methods CT data of jaw bone defect from patients were acquired and the images were segmented using threshold segmentation combined with region growing . The three dimensional model was reconstructed by Boolean operation. The individual 3D digital model was reconstructed with internal structure by combining with computer; preparing poly-lactic acid scaffold in virtue of 3D technology. Results Using the Mimics software, we successfully constructed a 3D digital reconstruction model of bone defect based on CT data. The constructed scaffold model with certain internal form and structure was matched with the bone defect of patients, and the constructed model was exported onto STL standard format, which may be in common use. Conclusion The 3D digital model of bone defect scaffolds may effectively be reconstructed based on the CT data using Mimics software and computer aided design.

OBJECTIVE To explore cell death type of lateral line hair cellsinduced by cisplatin in zebrafish. METHODS Zebrafish larva were incubated in 1mM cisplatin solution for 6 hrs to induce about 90%lateral line hair cells loss. Time lapse imaging was used to detect the morphology of cisplatin-incubated hair cells in wildtypezebrafish pre-labelled by live dyes Bodipy TR C5-ceramide and Sytogreen 24. TUNEL assay and In situ anti-active Caspase-3 antibody staining were performed to detect nuclei fragmentation and Caspase-3 activity respectively. RESULTS Compared to control group, hair cells condensationand nuclei fragmentation (P<0.05) were detected in cisplatin-incubated group, and active Caspase-3 activity was also observed after cisplatin addition. CONCLUSION Cisplatinmay induced zebrafish lateral line hair cells loss by Caspase-3-dependent apoptotic pathway.

Objective To establish a hyperacute rejection model in ABO-incompatible renal allotransplantation in nonhuman primates.Method ABO-incompatible renal transplantation was performed using blood group B cynomolgus monkeys as recipients and blood group A cynomolgus monkeys as donors.The transplants were distributed into 2 groups according to whether the recipient monkey was presensitized or not:(1) non-presensitized control group (n =1),not receiving any pretreatment; (2) KLH-conjugated blood group antigen A (KLH-A) presensitized group (n =3),being presensitized by subcutaneous injection of KLH-A 2 weeks prior to ABO-incompatible renal transplantation.The serum anti-blood group A antibody levels were measured using a FACS method.The graft survival time was observed and the pathologic studies were performed using the endpoint renal graft tissue samples.Result In non-presensitized control group,no hperacute rejection was observed during the surgery.With the traditional CsA triple therapy,the renal allograft survived was more than 30 days without obvious rejection,and the serum creatinine level was 263 μmol/L at day 30.After the presentization with KLH-A,recipient monkeys of KLH-A presensitized group had a markedly increased anti-A antibody levels and rapidly rejected the renal allografts from blood group A donors within 1 h after the reperfusion,which was demonstrated to be a hyperacute rejection with the pathologic studies.Conclusion The strategy of presensitization with KLH-conjugated blood group antigen significantly increases the corresponding blood group antibodies and allows the establishment of a hyperacute rejection model in ABO-incompatible renal allotransplantation in nonhuman primates.

Clinical laboratory undergraduate program was switched from medicine to medical technology,the changes of personnel training program compel universities to adjust the curriculum system.Six domestic known as 211 universities who have laboratory and biology undergraduate programs were scrutinized and compared.Overall,the proportion of general courses covers 30％ of the credit hours in both clinical laboratory and biology programs.Ratio of these general education curriculums to professional core courses is as high as 1.90∶1 in clinical laboratory program.Also,there were very strong medical features and very weak medical technology characteristics in the basic course in clinical laboratory program.It suggested that the curriculum system nowadays cant conform to the new personnel training objective.A novel system from abroad should be adopted to optimize clinical laboratory program accord with the principles and concepts of wide caliber training model.

Objective To detect the mutations in ATP2C1 gene of 5 sporadic patients with Hailey-Hailey disease (HHD).Methods Five sporadic patients with HHD collected from the outpatient clinic setting were recruited into this study with informed consent.Blood samples were taken from all patients and 100 unrelated human controls.and DNA was extracted from these samples.Mutation scanning was carried out for ATP2C1 gene by polymerase chain reaction (PCR) and direct sequencing.Results The diagnosis of all cases was confirmed by typical clinical manifestation,cutaneous pathology and immunofluorescence pathology.Five novel mutations.including a deletion mutation (2025delG),three missence mutations (L269R,C348R,A651D) and a non-sense mutation (Q259X) were identified in these cases.No mutations were detected in any of the 100 controls.Conclusion Five novel mutations in ATP2C1 gene have been identified for Hailey-Hailey disease.

Objective To investigate prenatal diagnosis and prognosis of fetus with hyperechogenic kidney.Methods Clinical data of 65 cases prenatally diagnosed with fetal hyperechogenic kidney in Peking University First Hospital between July,2009 and May,2015 were retrospectively analyzed.Results of fetal ultrasound screening and pregnancy outcomes were analyzed and Growth and development status of those babies were followed up until December,2015.Independent-sample-t,Chi-square or Fisher's exact test was applied for statistical analysis.Results Among the 65 cases,including 48(73.8％) bilateral and 17 (26.2％) unilateral,34 cases (52.3％) were diagnosed as non-isolated and 31 cases (47.7％) as isolated fetal hyperechogenic kidney.The primary associated malformations with non-isolated fetal hyperechogenic kidney included cardiac abnormality (14 cases,41.2％),urinary system abnormality (12 cases,35.2％),skeletal system abnormality (nine cases,26.5％),central nervous system abnormality (eight cases,23.5％) and Meckel-Gruber sydrome (one case,2.9％).Amniotic volume,the size and numbers of affected kidney between non-isolated and isolated groups showed no significant differences (all P＞0.05).Twenty out of the 65 cases (30.8％) received fetal karyotyping and one received non-invasive prenatal testing,and no abnormality was detected.Three cases received cord blood array comparative genomic hybridization with negative results.Pathogenic genes were found in two cases who received targeted exome capture with high throughput sequencing,including a TTC21B mutation in cord blood in one case and a HNF1β deletion mutation in peripheral blood after birth in the other.There were 23 (35.4％) terminations of pregnancy and 42 (64.6％) live births among which three died after birth.The rate of live birth was significantly higher in the isolated group than in the non-isolated group[87.1％(27/31) vs 44.1％(15/34),x2=13.101,P＜0.01].Of the fifteen live births in the non-isolated group,there were fourteen survived symptomfree except that one lost to follow-up.Of the 27 live births in the isolated group,follow up study revealed 23 symptom-free survivors,one lost,two neonatal deaths (one died of volvulus neonatorum,and the other due to unknown causes) and one death of renal and liver function failures at the age of two-and-a-half.ConclusionsFetal hyperechogenic kidney is an important prenatal ultrasound marker for congenital renal anomalies,and the prognosis of non-isolated fetal hyperechogenic kidney is poor.The current rate of abnormal karyotype in fetus with hyperechogenic kidney is very low.However,the rate of prenatal genes screening should be encouraged.

Objective To investigate esophageal motility characteristics in gastroesophageal reflux disease (GERD) patients with or without dysphagia by high-resolution manometry and 24 h esophageal pH monitoring.Methods From August 2012 to November 2015,GERD patients with symptoms of acid reflux and heart burn who received 24 h esophageal pH monitoring were collected.The differences in esophageal motility were further analyzed between the GERD patients with dysphagia and without dysphagia.Student's t test,x2 test and Fisher's exact test were performed for comparison analysis.Results A total of 194 patients received 24 h esophageal pH monitoring and diagnosed as GERD,and at the same period completed esophageal high-resolution manometry.Among them,there were 17 GERD patients (8.8％) with dysphagia and 177 patients (91.2％) without dysphagia.The main classification of esophageal motility disorder of GERD patients with dysphagia was severe esophageal motility disorders (5/ 17),but the motility type of GERD patients without dysphagia patients mainly was mild esophageal motility disorders (10.2％,18/177).The integrated relaxation pressure,residual pressure of lower esophageal sphincter (LES),and contraction range at 3 cm and 11 cm above LES of GERD patients with dysphagia were all higher than those of patients without dysphagia ((9.70±0.98) mmHg (1 mmHg=0.133 kPa) vs (7.02±0.30) mmHg,(12.75±1.35) mmHg vs (9.18±0.42) mmHg,(106.80± 11.97) mmHg vs (70.82±3.48) mmHg,(82.66±10.70) mmHg vs (56.93±3.11) mmHg),and the differences were statistically significant (t=2.601,2.488,2.887,2.308,all P＜0.05).Distal esophageal contraction integral score of GERD patients with dysphagia was significantly higher than that of GERD patients without dysphagia ((2 128.94±310.47) mmHg · cm · s vs (1 029.88±90.16) mmHg · cm · s),and the difference was statistically significant (t =3.400,P =0.001).However,residual pressure of upper esophageal sphincter was significantly lower than that of patients without dysphagia ((2.84±1.21) mmHg vs (6.18±0.38) mmHg,t=-2.650,P=0.009).Conclusions Esophageal motility disorder of GERD patients with dysphagia is severer than that of patients without dysphagia.High resolution esophageal manometry can provide objective evidence of esophageal dynamics of GERD patients,which can guide the diagnosis and treatment of GERD.