Rapid detection of pathogenic microorganisms is important to the prevention and control of diseases.Com-pared with traditional approaches, electrochemical DNA biosensors present great advantages in promising rapid, portable, sensitive and cost-saving detection of pathogens.In this review, the working principle of electrochemical DNA biosensors and the progress in detection of pathogens is introduced, the latest developments of DNA tetrahedron structure and new nano materials in electrochemical DNA biosensors are reviewed, and the challenges to and prospects of development in this field are also discussed.

Objective:To compare immune effects of hepatitis B-BCG combined vaccine and hepatitis B vaccine.Methods:The vaccines were administered to the guinea pig at 0, 1, 2 months. The tests were divided into three parts. The immune effects were compared in three kinds of the combined vaccine and hepatitis B vaccine(Part One), in three lots of the combined vaccine and hepatitis B vaccine(Part Two), in the group of combined vaccine and the group of hepatitis B vaccine and BCG(Part Three). After 1 month of each vaccine dose, serum specimens were measured for anti-HBs by ELISA.Results:The several studies have documented the serum anti-HBs concentritious in the group of combined vaccine in first dose were lower than those of the group of control, and the data showed no significantly difference. However, anti-HBs levels of the combined vaccine group in second vaccine dose and third vaccine dose were higher than those of the control group, and this difference was no longer statistically significant in group of combined vaccine and control, and among groups of combined vaccine.Conclusion:The immune efficacy of HBsAg in group of combined vaccine is similar to the group of hepatitis B vaccine in three doses immunization schedules.

Objective: To explore the relationship between nutritional status and puberty onset in boys, and to provide a reference for promoting the development of physical and mental health of boys. Methods: A total of 2 724 boys aged 7 to 12 years from grade 2 to 6 were recruited from Xiamen city by cluster sampling method in 2017. The nutritional status was assessed by physical examination, pubertal developmental status was evaluated by rating scales of Tanner and Prader orchidometer, and puberty timing was determined by the P25 age of puberty onset. The association between nutritional status and puberty onset was estimated by logistic regression model. Results: Pubertal onset was found in 29.0% of the boys and the incidence of early pubertal timing was 2.9%. The prevalence of puberty onset in wasting, normal weight, overweight and obesity boys was 19.6%, 28.7%, 34.4% and 31.5%, respectively. The age of puberty onset was significantly earlier in obese boys (F=3.23, P<0.05). The results of Logistic regression analysis showed that with the increase of BMI, the possibility of puberty onset and risk of early pubertal timing increased. After adjusting for confounding factors, the odds of puberty onset in boys with wasting decreased by 64.0% (OR=0.36, 95%CI=0.22-0.60), the possibility of puberty onset and risk of early pubertal timing in boys with obesity increased by 78.3% (OR=1.78, 95%CI=1.14-2.79) and 192.9% (OR=2.93, 95%CI=1.46-5.86), respectively. These relationships were more pronounced in boys of households with lower economic level (P<0.05). Conclusion BMI was positively correlated with puberty onset in boys, the odds of puberty onset and risk of early pubertal timing were significantly increased in obese boys, especially in those with low household economic level.

Cognitive dysfunction is the impairment of higher brain functions.Cognitive impairment caused by neuropsychiatric diseases has caused serious impact on patients'quality of life and the outcome of the disease.The transcranial alternating current stimulation(tACS)improves cognitive function by modulating neural oscillations of specific frequencies,affecting the release of neurotransmitters such as serotonin and dopamine,and enhancing local and distal synchronization of brain networks.Specific frequencies of tACS can improve the cognitive impairment caused by Alzheimer disease(AD),schizophrenia,and depression,among which the gamma and theta frequencies of tACS have the most significant effects on cognitive function.tACS has high safety and low operational difficulty,and has great potential to improve cognitive function.

Objective:To analyze differentially expressed microRNAs (miRNAs) and target genes in human respiratory epithelial cells (16HBE) after enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) infection using high-throughput sequencing.Methods:TargetScan and miRDB databases were used to predict the target genes of miRNAs that were both up-regulated or down-regulated after EV71 and CVA16 infection. The genes that were both up-regulated and down-regulated were screened out. GO and pathway analysis of the target genes were conducted to screen immune-related target genes and their corresponding miRNAs. The target genes and their corresponding miRNAs that were up-regulated or down-regulated in both immune-related GO and pathway were further screened. Some miRNAs and their target genes were selected for qRT-PCR verification.Results:There were 598 target genes of up-regulated miRNAs and 1 311 target genes of down-regulated miRNAs and 62 target genes that might be up-regulated or down-regulated simultaneously were screened out. The number of up-regulated target genes involved in immune-related GO and pathway were 17 and 13, respectively, and the number of corresponding miRNAs were 15 and 17, respectively. There were 58 and 47 down-regulated target genes involved in immune-related GO and pathway, respectively, and the number of corresponding miRNAs were 30 and 42, respectively. Three up-regulated target genes were involved in both immune-related GO and pathway and regulated by four miRNAs. Nine down-regulated target genes were involved in both immune-related GO and pathway and regulated by 13 miRNAs.Conclusions:This study was conducive to elucidate the host-pathogen interaction after EV71 and CVA16 infection, and provided reference for studying the pathogenesis of hand, foot and mouth disease.

Objective:To investigate whether coxsackievirus A 16 (CVA16) infection would affect the expression of N6-methyladenosine (m 6A) methylation-related proteins in human bronchial epithelial cells (16HBE), ICR suckling mice and SCRBA2 humanized mice and influence their subcellular localization. Methods:CVA16 was used to infect 16HBE cells at a multiplicity of infection (MOI) of 0.1 and mice at 10 7 CCID 50/ml. Changes in the expression of methyltransferases, demethylases and methylated reading proteins were analyzed by Western blot. Cellular localization of these proteins was observed using immunofluorescence. Results:The expression of m 6A methylation-related proteins was gradually reduced in CVA16-infected cells with time, but showed no obvious change in ICR suckling mice or SCRBA2 humanized mice. After infection, m 6A methylation-related proteins were redistributed in both the nucleus and cytoplasm and even degraded. Conclusions:CVA16 replication in host cells altered the expression and cellular localization of m 6A methylation-related proteins, which indicated that m 6A modification might be a new potential target for enterovirus therapy.

OBJECTIVE：To excavate the safety warning signals induced by azole antifungal agents ，including fluconazole ， ketoconazole，itraconazole and voriconazole after marketing ，and to provide references for rational drug use in the clinic. METHODS：Reporting odds ratio （ROR）data mining algorithm was used to investigate signals of adverse drug event （ADE）for fluconazole，ketoconazole，itraconazole and voriconazole from FDA Adverse Event Reporting System （FAERS）during January 1st，2004 to March 30th，2019. ROR data mining method was used to excavate the ADR signals of the drugs ，and main ADR involved in the safety information of azole antifungal agents instructions were analyzed. RESULTS ：A total of 27 831，5 712， 5 381 and 11 333 reports were picked out for fluconazole ，ketoconazole，itraconazole and voriconazole ，respectively. All of these drugs had exhibited high-risk signals detection by ROR ，including medical examination ，blood and lymphatic system disorders ， renal and urinary disorders ，endocrine diseases ，hepatobiliary disorders. The hepatotoxic-related ADR signals were mainly concentrated in fluconazole and voriconazole （fluconazole ROR ＝6.51，voriconazole ROR ＝14.65）；ADR detection results of Cushing’s-like syndrome （ROR＝24.86） and adrenal suppression （ROR＝44.06） by itraconazole showed high-risk signals ； ketoconazole and itraconazole had showed a strong ADR signal in adrenocortical dysfunction （ketoconazole ROR ＝15.64， itraconazole ROR ＝23.26），and the signal intensity of ketoconazole （ROR＝2.81）in skin and subcutaneous tissue disorders was significantly higher than that of other drugs . In addition ，hemorrhagic cystitis caused by fluconazole，itraconazole and voriconazole were not included in the drug instructions （fluconazole ROR ＝17.73，itraconazole ROR ＝31.43，voriconazole ROR ＝17.06）； netted green spot caused by fluconazole （ROR＝10.50）were not included in the drug instructions . CONCLUSIONS：Clinical staff should pay more attention to the differences in serious ADR related to fluconazole ，ketoconazole，itraconazole and voriconazole ； particularly some ADRs not mentioned in the drug instructions but have high incidence such as hemorrhagic cystitis caused by fluconazole，itraconazole，voriconazole and netted green spot caused by fluconazole ，as well as ADRs mentioned in the drug instructions but have abnormally high signal ，such as Cushing ’s-like syndrome and adrenal suppression caused by itraconazole .