Objective To evaluate the protective effectiveness of MPT64 and ESAT6 DNA vaccines against M. tuberculosis. Methods BALB/c mice were randomly divided into 14 groups and subjected to following treatments respectively, i.e. immunized with. ESAT6 (25?g)+MPT64 (25?g)(A), ESAT6(100?g)+IFN-?(100?g) (B), ESAT6 (75?g)+MPT64 (25?g)(C), ESAT6(100?g)+IL-12(100?g) (D), MPT64(100?g)+IL-12(100?g) (E), ESAT6 (25?g)+MPT64 (75?g)(F), MPT64 (100?g)(G), Pvax1 (H),ESAT6 (100?g)(I), ESAT6 (100?g)+MPT64 (100?g)(J), ESAT6 (50?g)+MPT64 (50?g)(K), MPT64(100?g)+IFN-?(100?g)(L), BCG(M ), and saline(N). Then they were infected with M. tuberculosis H37Rv via intravenous route. The pathological changes in the lung, liver, and spleen were observed after the infection. Results Eight weeks after the inoculation, there were only alveolar exudation and capillary hyperemia in the lung lesions in the mice of group N. In the mice of group M and J, main pathological changes included tuberculous granulomas consisting of numerous lymphocytes, macrophages, epithelioid cells and Langhans giant cells, and moderate hyperplasia in alveolar walls. The lung lesions of the other groups were similar, and both hyperplasia and exudate were found (A, B, C, D, E, G, H, I, K, L). No necrosis was found in all the above groups. There were hyperemia, dense lymphocytes infiltration in the portal area, and tuberculous granuloma in the liver in all the groups. No difference was found among all the groups. The pathological changes in spleen induced hyperplasia and fusion of splenic lymph nodule. The reactions in group M and J were stronger than that of the other groups. Conclusions MPT64 and ESAT6 DNA vaccines from M.tuberculosis could enhance immunity against M. tuberculosis, either they were used in combination with different dosages or with IL-12 or IFN-?. The vaccine used in group J showed the strongest effect in enhancing immunity, almost reaching that of combined use of BCG, IFN-? and IL-12.

Objective To identify a novel pathogenicity mutation of acid alpha‐glucosidase(GAA) gene in a Chinese family with two siblings affected with juvenile onset form glycogen storage disease Ⅱ(GSD Ⅱ) .Methods The clinical and family data of two siblings presenting recurrent respiratory tract infections ,respiratory failure associated with systemic muscle weakness ,were an‐alyzed and diagnosed with GSD Ⅱ by detecting alpha‐1 ,4‐glucosidase activity .DNA was extracted from peripheral blood of the proband ,younger brother and his parents .All 20 exons and the intron‐exon splice sites of GAA gene were amplified by polymerase chain reaction (PCR) .Mutations were detected by direct sequencing the PCR products .Results The younger brother was found to be compound heterozygous for two mutations in the GAA gene :c .1216G>A (p .Asp406Asn) missense mutation in the exon 8 from his father and c .1935C>A (p .Asp645Glu) missense mutation in the exon 14 from his mother .Conclusion The compound hetero‐zygous c .1216G>A and c .1935C>A mutations caused the juvenile onset form GSD Ⅱ characterized by dyspnea and cardiac hyper‐trophy .The novel c .1216G>A mutation may be related to the juvenile onset form GSD Ⅱ .

Objective To investigate the distribution of 3279 and 924 Foxp3 genotypes in Guangdong population and to explore the correlation between Foxp3 gene polymorphism and essential hypertention . Methods Two hundred and six essential hypertention patients and 291 healthycontrols from October 2013 to September 2014 in the third affiliated hospital of guangzhou medical university were enrolled in the study. The Foxp3 3279 and 924 genotypes was identified by PCR-SSP assay. The plasma lipid level and other risk factor were detemined in all subjects. The relationship between genotypes and pathogenesis of EH was analyzed. Results There were sigificant differences in frequecncies of allele and genotype distribution in Foxp3 3279 genotypes between the two groups. The frequecies of AC+CC and allele were significantly higher in the EH group than those in the control group (P<0.05). Result of logictics analysis showed that AC+CC genotype significantly increase the risk of EH (OR = 1.552,95%CI为1.021 ~ 2.357, P < 0.05), but the polymorphism of Foxp3 924 genotype frequecncy was not assosiated with EH. Conclusion The Foxp3 3279 gene polymorphisms is associated with EH . However, the Foxp3 924 gene polymorphisms is not associated with EH.

One new sesquiterpene was isolated from the fermentation broth of Streptomyces sp. and the structure was elucidated by spectral analysis as caryolane-1, 6beta-diol (1). An intermediate 1alpha, 6beta, 11-eudesmanetriol (2) in the biosynthesis of geosmin was also found in this strain which proved sequence for the reactions, especially bicyclization preceding dealkylation.

Objective To analyze the reasons for the withdrawal of the National Natural Science Foundation of China projects,adopt preventive measurements,to provide countermeasures for the project application and establish scientific integrity.Methods Search the official website of National Natural Science Foundation of China(http://www.nsfc.gov.cn/),and browse case processing decisions during the last five years,analyze the reasons for the withdrawal of projects and classify the scientific misconducts.Results We got 83 publicly accessible cases which involved 93 persons.There were 52 projects whose fund granting has been annulled,and 50 projects at the stage of application have been revoked due to scientific misconduct.The projects were withdrawn mainly due to the fraud peer review,accounting for 46.2％,the project applications were revoked mainly due to copying applications,accounting for 54.0％.Conclusions The countermeasures to prevent the scientific misconducts in the application process including:increase scientific research integrity propaganda;improve the construction of laws and regulations;improve the detection rate of scientific misconduct;give full play to the supervisory role of supporting institutions;increase the intensity of punishment;improve the selection and supervision system of experts;establish a credit management system during the whole process.

Objective To analyze the reasons for the retraction of journal papers after publishing,take preventive measures,provide countermeasures for establishing research integrity.Methods Search the PubMed Database (https://www.ncbi.nlm.nih.gov/pubmed/) with search type "Retracted Publication" [Publication Type] OR "Retraction of Publication" [Publication Type],from 2016/01/01 to 2017/06/01,to acquire the retracted publications,and to summarize the reasons for retraction.Results Initially extracted 1 098 results,and ultimately 895 papers were included in the analysis.The reasons for retraction were divided into two categories:unintentional errors and academic misconduct.The main reasons of academic misconduct were fabrication and falsification,accounted for 30.17％,followed by plagiarism,accounted for 20.22％.Conclusions Main reason for the retraction of journal papers was academic misconduct.We can establish scientific integrity through the following ways,such as strengthening the research ethics education and enhancing the awareness of research integrity;improving the scientific evaluation system and creating free atmosphere of scientific research;establishing long-term system of management,supervision and punishment of scientific research;taking rigorous review of manuscripts by editor.

Bone age is a quantitative representation of the skeletal development pattern.X-ray imaging of the wrist with the Greulich-Pyle method is commonly used to assess bone age in clinic.In adolescent children, the sensitivity and specificity of the the Greulich-Pyle method are not sufficient because the bones of the wrist are already mature.In contrast, epiphyseal morphological changes in the knee joint throughout adolescence can provide information for the assessment of bone age in adolescent children, and the feasibility of knee joint bone age assessment has been verified.With the application of artificial intelligence (AI) in the medical field, the accuracy of AI interpretation of bone age is also recognized.One of the important uses of bone age assessment in adolescent children is to predict the remaining growth potential.Based on knee images, exploring the use of AI to build a model for predicting residual growth potential is a more meaningful research direction for clinical purposes.This paper reviews the anatomical characteristics of the knee joint, the application of knee joint imaging and the research progress of AI in bone age assessment.

Objective Improve the ethical review models of multi-center clinical trial.Methods Analyze the ethical review models of multi-center clinical trial in China,and summarize advantages and disadvantages of the different methods.Then,clarify the development of ethical review methods of multi-center clinical trial in our hospital.Results Four methods were used to review the multi center clinical trial in China,including independent ethical review,central institutional ethical review,central review made by committee cooperation,collaborative review.Each method has its advantages and disadvantages.Collaborative review about multi-center clinical trial is adopted now in our hospital.Conclusions Using collaborative review model of multi-center clinical trial,the ethical review could achieve timely and uniformly.

Objective To explore the clinical features,primary lesions and prognosis of optic nerve metastases.Methods Seven patients (11 eyes) with optic nerve metastatic tumor diagnosed by the examinations of ophthalmology,laboratory and pathology in Chinese PLA General Hospital from April 2015 to September 2017 were included in this study.All patients underwent BCVA,flash VEP,OCT,orbital MRI,serum tumor marker,cerebral spinal fluid detection and PET-CT.Histopathological examination of primary or near superficial metastases was performed.The follow-up period was ranged from 16 to 44 months,with the mean of 23.0 ± 10.9 months.The clinical characteristics,primary tumor,imaging features,treatment and clinical prognosis in the patients were analyzed.Results Among 7 patients,there were 5 males and 2 females,with the mean age of 53.90± 14.99 years;3 patients with unilateral optic nerve involvement,4 patients with bilateral optic nerve involvement;5 patients (71.4％) first diagnosed in ophthalmology.Five patients (45.5％) were misdiagnosed as optic neuritis,optic disc edema in 6 eyes (54.5％).All of them appear loss of visual acuity,including 8 eyes (72.7％) with BCVA＜ 0.1,2 eyes (18.2％) with BCVA 0.1-0.5,1 eye (9.1％) with BCVA ＞ 0.5.MRI results show that 1 patient with intraorbital segment,1 patient with internal segment of optic canal,4patients with intracranial segment,1 patient with intracranial segment and optic chiasma involved simultaneously,4 patients involving surrounding tissue.There were 4 patients (57.1％) with lung cancer,2 patients (28.6％) with kidney cancer,1 patient (14.3％) with gastric cance;6 patients (85.7％) with metastasis from other sites,2 patients with brain metastasis (1 patient with meningitis carcinomatosa).There were 2 patients (28.6％) with previous primary cancer surgery.After diagnosis,1 patient received chemotherapy,1 patient received radiotherapy,5 patients gave up treatment.At the end of follow-up,1 patient (1 eye) of chemotherapy with BCVA increased by 2 line;1 patient (2 eyes) of radiotherapy with no change in BCVA;of the 5 patients who gave up treatment,1 patient died of disease,1 patient lost follow-up,and 3 patients (4 eyes) had no change in BCVA.Conclusions With atypically clinical manifestations,the optic nerve metastases easily misdiagnosed as optic neuritis,and with poor therapeutic effect.Primary lesions are mostly found in lung cancer.

Objective To assess the performance of pediatric clinical illness score (PCIS), pediatric risk of mortality scoreⅢ(PRISMⅢ), pediatric logistic organ dysfunction score 2 (PELOD-2), and pediatric multiple organ dysfunction score (P-MODS) in predicting mortality in critically ill pediatric patients. Methods The data of critically ill pediatric patients admitted to Pediatric Intensive Care Unit (PICU) of First Affiliated Hospital of Sun Yat-Sen University from August 2012 to May 2017 were retrospectively analyzed. The gender, age, basic diseases, the length of PICU stay were collected. The children were divided into survival group and non-survival group according to the clinical outcome during hospitalization. The variables of PCIS, PRISMⅢ, PELOD-2, and P-MODS were collected and scored. Receiver operating characteristic (ROC) curve was plotted, the efficiency of PCIS, PRISMⅢ, PELOD-2, and P-MODS for predicting death were evaluated by the area under ROC curve (AUC). Hosmer-Lemeshow goodness of fit test was used to evaluate the fitting degree of each scoring system to predict the mortality and the actual mortality. Results Of 461 critically ill children, 35 children were excluded because of serious data loss, hospital stay not exceeding 24 hours, and death within 8 hours after admission. Finally, a total of 426 pediatric patients were enrolled in this study. 355 pediatric patients were survived, while 71 were not survived during hospitalization, with the mortality of 16.7%. There was no significant difference in gender, age, underlying diseases or length of PICU stay between the two groups. PCIS score in non-survival group was significantly lower than that of survival group [80 (76, 88) vs. 86 (80, 92)], and PRISMⅢ, PELOD-2 and P-MODS scores were significantly increased [PRISMⅢ: 16 (13, 22) vs. 12 (10, 15), PELOD-2: 6 (5, 9) vs. 4 (2, 5), P-MODS: 6 (4, 9) vs. 3 (2, 6), all P < 0.01]. ROC curve analysis showed that the AUCs of PCIS, PRISMⅢ, PELOD-2, and P-MODS for predicting death of critical ill children were 0.649, 0.731, 0.773, and 0.747, respectively. Hosmer-Lemeshow test showed that PCIS predicted the mortality and the actual mortality in the best fitting effect (χ2= 7.573, P = 0.476), followed by PELOD-2 and P-MODS (χ12 = 9.551, P1= 0.145; χ22 = 10.343, P2= 0.111), while PRISMⅢ had poor fitting effect (χ2= 43.549, P < 0.001). Conclusions PRISMⅢ, PELOD-2 and P-MODS can discriminate between survivors and moribund patients well, and assessing the condition of critically ill pediatric patients with relatively accuracy. PCIS was the best fitting effect in predicting mortality and actual mortality, followed by PELOD-2 and P-MODS, while PRISMⅢ had poor fitting effect.