【Objective:】 To analyze and explore the key points of the ethical review of real-world research in pediatric population, and to provide reference for ethical review of real-world research in pediatric population. 【Methods:】 According to the characteristics of real-world research and pediatric clinical trials, the review points of real-world research in pediatric population were analyzed and discussed in comparison with the principles and focus of ethical review in general clinical research. 【Results:】 The ethics committee should pay particular attention to the review of informed consent, privacy protection, risk benefit assessment, cost and compensation, and should also take into account the research design, data governance, research conflicts of interest, research registration and publication, etc., and conduct scientific and reasonable ethical review of real-world research in pediatric population. 【Conclusion:】 Clinical trials in pediatric population should have stricter and scientific ethical review, which can not only protect the interests of vulnerable groups of minors, but also standardize real-world research in pediatric population and promote the healthy development of pediatric clinical research, so as to better protect children and promote their health.

Objective:To investigate the expression of hsa_circ_0000437 in the serum of patients with gastric cancer and its clinical value.Methods:The serum samples from 80 patients (57 males and 23 females) with pathologically confirmed gastric cancer (GC), 50 gastric benign disease (28 males and 22 females) and 80 healthy controls (46 males and 34 females) were collected from October 2018 to December 2020 in Affiliated Hospital of Nantong University.Serum samples from 35 of 80 gastric cancer patients after operation were collected. The expression of serum hsa_circ_0000437 was determined by real-time fluorescent quantitative PCR (RT-qPCR). Serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA 199) and carbohydrate antigen 724 (CA724) were determined by chemiluminescence method.Comparisons of serum hsa_circ_0000437 between groups were performed by Mann-Whitney U test.The correlation between serum expression of hsa_circ_0000437 in gastric cancer patients and its clinical pathological characteristics was performed by χ 2 test.Receiver operating characteristic (ROC) curve and the area under the curve of ROC (AUC) were used to evaluate their diagnosis efficiency. Kaplan-Meier survival curve analysis was used to analyze the relationship between the expression level of serum hsa_circ_0000437 and the prognosis of patients. Results:The relative expression of hsa_circ_0000437 in GC, gastric benign disease, healthy controls were 2.252 (1.235, 4.765), 1.598(1.139, 1.982) and 1.000 (0.818, 1.385) respectively.The relative expression of hsa_circ_0000437 in GC was significantly higher than that in gastric benign disease ( P<0.001) and healthy controls ( P<0.001). The difference between gastric benign disease and healthy controls was also statistically significant ( P<0.001).The differences of serum hsa_circ_0000437 expression in GC patients between T stage, N stage, and tumor differentiation were statistically significant. The AUC of hsa_circ_0000437, CEA, CA199 and CA724 in GC patients were 0.863, 0.619, 657 and 0.608 respectively compared with healthy controls. The AUC of above four-parameter panel was 0.892 and the sensitivity was up to 97.5% (78/80). Kaplan-Meier survival curve showed that the overall survival rate of patients with high serum hsa_circ_0000437 expression was significantly lower than that of patients with low expression ( P=0.008). Conclusion:Serum hsa_circ_0000437 could be a biomarker for the auxiliary diagnosis and prognosis of GC.

Objective:To evaluate the current status of the registered pediatric drug or vaccine clinical trials in China for the purpose of providing a reference for the development of pediatric clinical trials in China.Methods:We collected the data about registered pediatric clinical trials that were conducted from September 6, 2013(Mandatory registration start date) to September 6, 2019 (Cut-off date) at Chinadrugtrials.org.cn platform. The survey items included trial name and number, drug classification, sponsor′s information, current trial status, completion status, etc. The clinical trials were categorized by drug group (includes chemical medicine, traditional Chinese medicine and natural medicine, biological products) and by vaccine group.Results:During the six years 349 pediatric clinical trials were registered on the platform, including 162 pediatric drug trials and 187 vaccine trials. The numbers of chemical drugs and biological products registered in 2018 were 23 and 11, respectively, the highest in the history. The number of pediatric clinical trials of traditional Chinese medicine and natural medicine was 11 in 2014, but from 2015 to 2018 only 2 to 4 trials were registered each year. The overall completion rates of the registered drug and vaccine clinical trials were 22.8% (37/162) and 41.7%(78/187), respectively. Only 42 international multicenter pediatric clinical trial projects were registered on the platform. The numbers of drug and vaccine phase Ⅰ clinical trials were 4 and 46, respectively. Thirty-six pediatric endocrine system agent clinical trials were carried out, with the largest number of all the drug categories registered on the platform.Conclusions:In recent years the number of registered pediatric drug and vaccine clinical trials increased in China. However, the number is still very limited. It is urgent to further promote the development of pediatric clinical trials.

Objective:To investigate the expression and its diagnostic value of long-chain non coding RNA (lncRNA) and colon cancer-related transcript-2 (CCAT2) in serum of patients with cervical cancer (CC).Methods:Serum samples of 100 CC patients, 60 CIN patients and 80 healthy people enrolled by Nantong Tumor Hospital from January 2016 to June 2017 were collected.The expression levels of CCAT2 in sera of CC patients and their corresponding postoperative patients, CIN patients and healthy controls were detected by real-time fluorescent quantitative PCR (RT-qPCR). The correlation between CCAT2 and clinicopathological features, as well as the traditional auxiliary diagnostic makers of CC, such as carbohydrate antigen 125 (CA125) and squamous cell carcinoma antigen (SCC) was analyzed. The working characteristic curve (ROC) of the subjects was used to evaluate the CCAT2 pair in the auxiliary diagnostic value of cervical cancer.Results:The relative expression levels of serum CCAT2 in patients with cervical cancer, patients after operation, patients with CIN and healthy controls were1.689 (0.616, 4.776), 1.018 (0.227, 3.328), 0.815 (0.453, 1.266) and 0.740 (0.271, 1.670), respectively.The relative expression of CCAT2 in cervical cancer patients was significantly higher than that in post-operative patients, CIN patients and healthy controls. The difference was statistically significant( t=6.999,8.193,9.345, P<0.001).There was no significant difference in the relative expression of CCAT2 between CIN patients and healthy controls ( t=0.327, P>0.05).The relative expression of CCAT2 in serum of cervical cancer patients had no significant difference in age 1.636(1.000,2.370),1.705(1.095,2.243) (χ 2=0.137, P=0.712) and menopause 1.672(1.059,2.342),1.659(1.068,2.298) (χ 2=0.000, P=1.000), but had significant difference with tumor size expression1.189(0.916,1.725),2.019(1.537,2.497)(χ 2=17.508, P=0.000),International Federation of Obstetrics and Gynecology (FIGO) staged expression stage 0.993(0.779,1.266),2.056(1.547,2.549),3.987(3.699,4.275)(χ 2=36.075, P=0.000) and lymph node metastasis 1.434(1.007,2.251),2.019(1.731,3.098) (χ 2=8.634, P=0.003). There was no correlation between the relative expression of serum CCAT2 and CA125 ( r2=0.003, P=0.563) and SCC (r 2=0.128, P=0.000).The diagnostic efficacy of serum CCAT2, CA125 and SCC in cervical cancer patients was analyzed by ROC curve. When compared with CIN patients, the areas under the curve were 0.890, 0.549 and 0.744, respectively. When compared with healthy patients, the areas under the curve were 0.857, 0.650 and 0.758, respectively. Conclusions:The level of serum CCAT2 in patients with cervical cancer is significantly higher than that in patients with cervical cancer, CIN patients and healthy controls. Serum CCAT2 may be a relevant marker for the diagnosis and prognosis of cervical cancer.

Objective To analyze the identification, drug resistance and clinical significance of a rare bacterium of Bordetella holmesii ( B. holmesii) to improve its detection and clinical diagnosis and treat-ment. Methods A strain isolated from a bacteremia case was identified by bacterial culture, biochemical tests and 16S rRNA gene sequencing. Mega 7. 0 software was used to conduct a similarity analysis of 16S rRNA gene sequences between the type strains of Bordetella spp. and the isolate, and then a phylogenetic tree was constructed. Antibiotic resistance of the isolate was determined by E-test. Changes in bacterial growth were measured after adding different concentrations of riboflavin or its inhibitor lumiflavin to the cul-ture medium. Results B. holmesii ABD2 was the pathogen causing bacteremia in the immunocompetent pa-tient. It was deposited under the number of CGMCC 1. 13721 in China General Microbiological Culture Col-lection Center (CGMCC), and the 16S rRNA gene sequences were deposited in National Center for Biotech-nology Information ( NCBI) with the accession number of KT828544. 1. Unrooted tree showed that the B. holmesii strain was highly homologous with B. pertussis. Antibiotic susceptibility test showed that the mini-mum inhibitory concentrations ( MIC) of piperacillin, ceftazidime, cefepime, imipenem, meropenem, cipro-floxacin, levofloxacin, gentamicin, amikacin, erythromycin, tetracycline and polymyxin B against the isolate were low, while the MIC values of cefazolin, cefuroxime, cefoxitin, cefotaxime, aztreonam and trime-thoprim-sulfamethoxazole were high. Riboflavin accelerated the growth of B. holmesii ABD2, while its inhibi-tor lumiflavin had an inhibitory effect. Conclusions As B. holmesii is hard to isolate and identify, limited clinical, microbiological and epidemiological data are available. It is an under-recognized pathogen with a considerable amount of information that remains to be studied.

Non-coding RNAs (ncRNAs) are genomic transcripts that do not encode proteins.They are also closely associated with tumor initiation and progression,as they play regulatory roles in gene transcription,post-transcription,and translation.Moreover,ncRNAs may enter circulatory system in the form of microvesicles or exosomes,or in combination with protein.The circulating ncRNAs are stable and widely existed in body fluids such as blood and urine.Certain circulating ncRNAs are differentially expressed in tumors,suggesting that they have potential value as novel tumor biomarkers.This article briefly reviews the progress of circulating microRNA (miRNA),long non-coding RNA (lncRNA) and circular RNA (circRNA) as breast cancer biomarkers,and discusses the clinical value of circulating ncRNA as a novel biomarker for breast cancer diagnosis and prognosis.

The initiation of tumor is a complex process with multi-factor participation, particularly the activation of oncogenes and/or inactivation of tumor suppressor genes. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis. Additionally, as a metabolic process in cells, autophagy also contributes greatly to differentiation, metastasis and chemoresistance of tumor cells, and has become a central topic in recent years. The understanding of connection between lncRNAs and autophagy as well as their mechanisms underlying tumorigenesis, can provide new ideas for the diagnosis and treatment of tumors.

Objective: To analyze the auxiliary diagnostic value of prostate cancer-associated non-coding RNA transcript1(PCAT-1) in serum of colorectal cancer(CRC) patients. Methods: The serum samples were collected from 73 patients with CRC who underwent surgical treatment and were diagnosed by pathology, 54 patients with colorectal polyps and 62 healthy controls at the Affiliated Hospital of Nantong University from October 2015 to January 2017. The serum level of PCAT-1 in CRC patients, colorectal polyps and healthy controls were measured by quantitative real-time polymerase chain reaction, respectively. The relationship between the level of PCAT-1 and the clinical pathologic feature was analyzed. Receiver operating characteristic curve(ROC) was used to evaluate the diagnosis value of PCAT-1, carcinoembryonic antigen(CEA), carbohydrate antigen 199 (CA199) alone and the combination of one of them in CRC. Results: The relative expression of PCAT-1 was 2.190 0(0.852 5, 6.715 0), 0.586 5(0.331 8, 1.697 0), 0.530 0(0.127 5, 0.957 5) respectively in CRC patients, colorectal polyps and healthy controls. The expression level of serum PCAT-1 in CRC patients was not related to the age (U=593, P=0.753 3), sex (U=536, P=0.390 8), tumor size (U=549, P=0.557 2) and location (U=584, P=0.426 7), but there was related to the degree of tumor differentiation (U=30, P=0.038 4) and tumor staging (U=399, P=0.005 0). ROC curve was used to analyze the expression of serum PCAT-1, CEA and CA199 for the diagnostic efficiency of CRC. The area under the curve(AUC) of ROC were 0.836, 0.756, 0.493 respectively in comparing CRC patients with healthy controls. The sensitivity of three joint tests was 93.2%(68/73), which was higher than that of single index. The area under the curve of ROC were 0.739, 0.673, and 0.515 respectively in comparing CRC patients with colorectal polyps. The sensitivity of three joint tests was 95.9%(70/73), which was higher than that of single index. Conclusions PCAT-1 maybe has auxiliary diagnosis of CRC. The combination of PCAT-1, CEA and CA199 remarkably improved the diagnostic efficacy of CRC.(Chin J Lab Med, 2018, 41: 514-518)

Objective: To explore the diagnostic value of serum cell-free DNA (cfDNA) concentration and integrity for esophageal carcinoma. Methods: Venous blood samples from 68 patients with esophageal cancer, 36 patients with benign esophageal lesions and 45 healthy subjects were collected. Circulating cfDNA was verified through quantitative real-time PCR (Alu-qPCR) using Alu-115 and Alu-247 primers. DNA integrity index was calculated as the ratio of Alu-qPCR results (Alu247/115). Concentrations of carcino-embryonic antigen (CEA) and squamous cell carcinoma associated antigen (SCC) were detected by chemiluminescence analyzer assay. Statistical analysis was performed using Mann-Whitney U test, Kruskal-Wallis H test and Spearman correlation test. The Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of each index to esophageal carcinoma. Results: The median absolute serum Alu115 and the Alu247/115 index (1 162.0 ng/ml, 0.57) in esophageal cancer group were significantly higher than those in benign esophageal disease group (496.7 ng/ml, 0.43) and in healthy control group (432.3 ng/ml, 0.42) (all P<0.01, respectively). The Alu115 and Alu247/115 index of serum DNA in benign esophageal disease group were no statistically different from those in the healthy control group (all P>0.05, respectively). The levels of cfDNA and its integrity were not significantly correlated with age, gender, tumor differentiation, or disease stage according to American Joint Committee on Cancer (AJCC) staging system in the esophageal cancer group (all P>0.05). The serum Alu247/115 index of Stage Ⅲ patients was higher than that of Stage Ⅰ~Ⅱ patients(P<0.05). The serum Alu247/115 index of Stage Ⅳ was higher than that of Stage Ⅲ(P<0.05). In the esophageal cancer group, both of serum Alu115 and Alu247/115 index had no correlation with CEA or SCC (all P>0.05). The area under the ROC curve (AUC) of Alu115 and Alu247/115 index were 0.867 and 0.854, respectively, which were both higher than that of CEA (0.622) and SCC (0.753). The addition of Alu115 or Alu247/115 index to CEA and SCC detection increased the sensitivity of the diagnosis of esophageal cancer by 95.6% and 94.1%, respectively. Conclusions The detection of serum cfDNA concentration and integrity is helpful to the early diagnosis and monitoring of esophageal cancer. Their diagnostic value of esophageal cancer is better than that of the traditional tumor markers CEA and SCC.

[Objective]To compare and contrast the dosimetry between Tomo planning and BrainLab planning for lung metasta-ses in stereotactic body radiation therapy(SBRT).[Methods]Four Patients with one,two,three and four metastases were selected. The PTV is 2.89 ± 1.15 cm3. Two plannings with total dose of 50 Gy to cover 95% of PTV ,5 Gy/Fraction and 10 fractions were designed using Tomo planning system and BrainLab planning system respectively. The DVH curves of spinal cord ,both lungs and normal tissue were compared. The conformity index andhomogeneityindex were analyzed as well.[Results]The homogeneity index (HI)and conformity index(CI)of the targets in Tomo planning system were 1.0314 ± 0.0700 and 0.687 ± 0.075,respectively. In BrainLab planning system the HI and CI of the targets were 1.0764 ± 0.1241 and 0.571 ± 0.042,respectively. To HI the P value in T test was less than 0.01 and the HI was better in Tomo than BrainLab and so was CI. The dose to spinal cord was higher in BrainLab planning system than that in Tomo. The dose to nomal tissue and both lungs were not different in the two planning systems and V20 of lung is as small as 10%.[Conclusions]For small volume lung metastases which longest diameter were less than 4 cm,the tomotherapy should be better choice.