Growth differentiation factor-15 (GDF-15) is a distant branch of the transforming growth factor-β (TGF-β) superfamily. Recent studies indicate that GDF-15 plays important physiological roles and has clinical implication in the initiation and development of various cardiovascular diseases. GDF-15 can both be used as a biomarker for the evaluation of cardiovascular disease occurrence and progression and a predictor for the risk stratification and long-term prognosis of cardiovascular diseases. The purpose of this review is to illustrate the latest research progress of GDF-15 in atherosclerosis and acute coronary syndrome obtained through the clinical research and basic experiments in cardiovascular diseases, to provide evidence for the selection of GDF-15 as useful biomarkers in the diagnosis and treatment of cardiovascular diseases.

Objective:To investigate the prevalence and genetic characteristics of human adenovirus (HAdV) in healthy children and diarrheal children in Beijing.Methods:A total of 1 834 fecal samples were collected from diarrheal children younger than 6 years old in outpatients from January, 2015 to December, 2017 and from healthy children with the same age group from May, 2016 to February, 2017. The hexon and fiber genes of HAdV were detected for genotyping and the sequences analysis, respectively.Results:The detection rate of HAdVs in healthy children (1.5%, 8/536) was significantly lower than that in children with diarrhea (7.4%, 96/1 298) ( χ2=23.62, P<0.001). HAdV-41 was the dominant type detected both in the healthy children and diarrheal outpatients. There was no gender difference in HAdV-positive children with diarrhea. Except for newborns with no positive case, there was no difference in the detection rate of HAdV among the other age groups. There was no obvious seasonality of HAdV prevalence. Phylogenetic analysis showed that HAdV-41 strains circulating in Beijing belonged to three evolutionary branches, and strains with 15-amino acid truncated in the shaft of fiber were found. Conclusions:HAdV was one of the important pathogens causing diarrhea in children in Beijing from 2015 to 2017, with HAdV-41 as the predominant type.

Objective:To investigate the molecular epidemiology of norovirus associated with pediatric acute gastroenteritis in Beijing under the Working Mechanism for Joint Prevention and Control of the Epidemic in 2020.Methods:This was a retrospective, repeated cross-sectional study. Fecal or vomit samples (1 213 cases) were collected from children visited the Capital Institute of Pediatrics Affiliated Children′s Hospital for acute gastroenteritis from January 1 to December 31, 2020. First, real-time reverse PCR (RT-PCR) was used to screen the samples for norovirus, and then RdRp gene and capsid gene VP1 of norovirus-positive samples were amplified by conventional RT-PCR for genotyping based on the nucleotide sequence. The χ 2 test was used to compare the positive rates and genotypes of norovirus among different specimen types, genders of children, and different age groups. Results:Among the 1 213 samples were collected, 215 samples were positive for norovirus, with a positivity rate of 17.7% for the whole year. The peak of norovirus infection observed mainly in the cold seasons, as the positive rates were 28.6% (18/63), 26.2% (16/61), 22.8% (77/338) and 17.1% (89/520) in January, October, November and December, respectively. The positive rate of norovirus in fecal sample was significantly higher than that in vomit sample (χ 2 = 9.692, P<0.01). There was no significant difference between genders (χ 2=0.041, P>0.05), but significant difference was found between age groups with the highest rate in the 6-48 months group (χ2=103.112, P<0.01). Three genogroups (GⅠ, GⅡ and GⅨ) of the circulating virus were detected by G-gene typing, and GⅡgenogroup was predominant, accounting for 98.5% (196/199). Among the GⅡ positive samples, genotype GⅡ.4 Sydney (55.1%, 108/196) was the most common, followed by GⅡ.2 (29.6%, 58/196), while the GⅡ.3 norovirus (10.2%, 20/196) which was common in previous years was not as much as before. Based on the P-type, GⅡ.P16 was predominant (61.5%, 96/156), followed by GII.P31 (19.9%, 31/156). The dual genotyping revealed that GⅡ.4 Sydney [P16] (36.4%, 56/154) and GⅡ.2 [P16] (24.7%, 38/154) were predominant. Conclusion:The prevalence of norovirus in children in 2020 in Beijing is not much different from those of the previous years, but the genotypes composition has changed significantly, and there are multiple genotypes circulating simultaneously.

Objective:To investigate the spectrum of pathogenic agents in pediatric patients with acute respiratory infections (ARI) during the outbreak of coronavirus infectious diseases 2019 (COVID-19).Methods:Three groups of children were enrolled into the prospective study during January 20 to February 20, 2020 from Capital Institute of Pediatrics, including children in the exposed group with ARI and epidemiological history associated with COVID-19 from whom both pharyngeal and nasopharyngeal swabs were collected, children in the ARI group without COVID-19 associated epidemiological history and children in the screening group for hospital admission, with neither COVID-19 associated epidemiological history nor ARI. Only nasopharyngeal swabs were collected in the ARI group and screening group. Each group is expected to include at least 30 cases. All specimens were tested for 2019-nCoV nucleic acid by two diagnostic kits from different manufacturers. All nasopharyngeal swabs were tested for multiple respiratory pathogens, whilst the results from the ARI group were compared with that in the correspondence periods of 2019 and 2018 used by t or χ 2 test. Results:A total of 244 children were enrolled into three groups, including 139 males and 105 females, the age was (5±4) years. The test of 2019-nCoV nucleic acid were negative in all children, and high positive rates of pathogens were detected in exposed (69.4%, 25/36) and ARI (55.3%, 73/132) groups, with the highest positive rate for mycoplasma pneumoniae (MP) (19.4%, 7/36 and 17.4%, 23/132, respectively), followed by human metapneumovirus (hMPV) (16.7%, 6/36 and 9.8%, 13/132, respectively). The positive rate (11.8%, 9/76) of pathogens in the screening group was low. In the same period of 2019, the positive rate of pathogens was 83.7% (77/92), with the highest rates for respiratory syncytial virus (RSV) A (29.3%, 27/92), followed by influenza virus (Flu) A (H1N1) (19.6%, 18/92) and adenovirus (ADV) (14.1%, 13/92), which showed significant difference with the positive rates of the three viruses in 2020 (RSV A: χ 2=27.346, P<0.01; FluA (H1N1): χ 2=28.083, P<0.01; ADV: χ 2=7.848, P=0.005) . In 2018, the positive rate of pathogens was 61.0% (50/82), with the highest rate for human bocavirus (HBoV) (13.4%, 11/82) and followed by ADV (11.0%, 9/82), and significant difference was shown in the positive rate of HBoV with that in 2020 (χ 2=6.776, P=0.009). Conclusions:The infection rate of 2019-nCoV is low among children in Beijing with no family clustering or no close contact, even with epidemiological history. The spectrum of pathogens of ARI in children during the research period is quite different from that in the previous years when the viral infections were dominant. MP is the highest positively detected one among the main pathogens during the outbreak of COVID-19 in Beijing where there is no main outbreak area.

Influenza is one of the most common and widespread respiratory diseases in humans.In addition to pose a serious threat to the susceptible and high-risk population,influenza has an important impact on public health.Rapid and accurate diagnosis of influenza virus infections is essential for administrating prompt antiviral treatments and undertaking effective prevention and control measures during seasonal epidemics and pandemics,which to reduce morbidity and mortality associated with influenza virus infections.Several different approaches are currently available for diagnosis of influenza infections in humans,including virus isolation,antigen detections,nucleic acid amplifications,etc.New diagnostic methods are being developed to overcome the limitations of some traditional detection methods.Here is an overview of diagnostic techniques for influenza virus infection.

Breast cancer is the most common spontaneous malignancy in women, causing a serious threat to women's health. Experimental animal models have been important research tools in bringing insights into the related mechanisms of breast cancer, as well as in delivering improved therapies for the disease. To reveal the pathogenesis of various breast cancers and facilitate the development of new drugs,ideal animal models of breast cancer should share some common tumor molecular characteristics and biological behavior with that of human breast cancer. In this review,five types of experimental animal breast cancer models were included, which may provide a basis for research on diagnosis and treatment of human breast cancer.

Objective: To analyze and compare the epidemiological features of prevalent influenza A viruses in children in Beijing during 13 consecutive surveillance seasons from 2004 to 2017. Methods: This was a repeated cross section study. Throat swabs were collected weekly from children with influenza-like illnesses (ILI) who presented to the outpatient/emergency department of Children's Hospital, Capital Institute of Pediatrics during the period from September, 2004 to August, 2017. All of the specimens were inoculated into Madin Darby canine kidney (MDCK) cells to isolate influenza viruses followed by identifying different types of influenza viruses with reference antisera by hemagglutination-inhibition assay. Descriptive statistics, t test and chi-square test were used to analyze the characteristics of prevalent influenza and characteristics of children infected with different types of influenza viruses. Results: Out of 10 984 specimens from ILI tested for influenza viruses, 1 052 (9.6%) were positive for influenza A viruses, and the positive rate was higher than that of influenza B viruses (6.7%, 741/10 984). Out of 1 052 cases positive for influenza A viruses, 70 cases of seasonal H1N1, 302 cases of 2 009 pandemic H1N1 and 680 cases of H3N2 were identified. The mean age of children with influenza A was (4.2±2.9) years, in whom 55.5% (584/1 052) were male. The mean age of children infected with seasonal H1N1, 2009 pandemic H1N1 and H3N2 was (4.6±2.1) , (4.3±3.1) and (4.2±2.9) years, respectively. There was no significant difference in the mean age among children infected with different subtypes of influenza A viruses (seasonal H1N1 vs. H3N2: t=1.139, P=0.255; 2009 pandemic H1N1 vs. H3N2: t=0.631, P=0.528; seasonal H1N1 vs. 2009 pandemic H1N1: t=0.720, P=0.472), while the mean age of children with influenza B was higher than that of the patients with influenza A ((5.2±2.7) vs. (4.2±2.9) years, t=7.120, P=0.000). The infection rate of influenza A in children with each age group was significantly different from that of influenza B. The infection rate of 2009 pandemic H1N1 and H3N2 increased with age, except for the patients of 0-6 months. Meanwhile, the infection rate of H3N2 in children aged 6 months to 12 years was higher than that of seasonal H1N1 and 2009 pandemic H1N1 (all P<0.05). The influenza A epidemic peaked earlier than that of influenza B when the positive rate of influenza A was higher than that of influenza B, and vice versa. After 2009, circulating strain was substituted by 2009 pandemic H1N1 virus with higher positive rate, while previous seasonal H1N1 had not been detected. The 2009 pandemic H1N1 circulated at high level in two consecutive seasons, which was followed by low level in next season. H3N2 epidemic peaked mostly in winter and spring each year, however, the epidemic wave of H3N2 with high virulence occurred so early in the summer in the year of 2009 H1N1 pandemic. Conclusions The characteristics of prevalent influenza A viruses in children were different among 13 surveillance seasons from 2004 to 2017 in Beijing. The 2009 pandemic H1N1 and H3N2 became the predominant strains of influenza A virus.

Objective: To understand the epidemiological and etiological characteristics of enterovirus (EV)-associated diseases among children in Beijing from 2010 to 2016. Methods: This was a repeated cross-sectional study. The throat swabs were collected from children with probable EV-associated diseases at the Children' s Hospital Affiliated to Capital Institute of Pediatrics from 2010 to 2016. The samples were sent for pan-EV, enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) detection by real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR) . The viral types of non-EV-A71 and non-CV-A16 EV-positive samples were identified using modified RT-PCR and sequencing with CV-A6, EV-A/B group and 5 'UTR universal primers. The constituent ratios of the prevalence of different EV types in different age and gender groups were compared. Results: Of the 2 703 throat swabs, 1 992 (73.7%) samples were positive for EV, including EV-A71 (19.1%, 516/2 703), CV-A16 (24.3%, 658/2 703), CV-A6 (22.2%, 600/2 703), CV-A10 (4.5%, 122/2 703) and other types of EV (3.5%, 95/2 703). There was 1 case of EV-A71 and CV-A16 co-infection. The positive detection rate of EV-A group (excluding EV-A71, CV-A16, CV-A6 and CV-A10) increased from 11.3% (7/62) to 95.2% (59/62) after using the modified VP1-specific primers and PCR amplification conditions. During the period between 2010 and 2012, CV-A16 and EV-A71 predominated in EV-positive samples. However, CV-A6 accounted for 60.7% (68/112) in 2013, much higher than CV-A16 (23.2%, 26/112) and EV-A71 (12.5%, 14/112). In 2014, EVs were mainly of CV-A16 and EV-A71, but CV-A6 was the predominant type in 2015 (68.2%, 232/340) and in 2016 (38.6%, 151/391). The epidemic season of EVs was mostly from April to August, but CV-A6 showed a small epidemic peak from October to November. The male-to-female ratio of EV-positive patients was 1.50∶1, and EV-associated diseases mostly occurred in children under 5 years of age. Younger children were more susceptible to CV-A6 than to EV-A71 and CV-A16. Conclusions From 2010 to 2016, there was a significant change in the spectrum of EVs in children with EV-associated diseases in Beijing. Since 2013, non-EV-A71 and non-CV-A16 increased, and CV-A6 gradually became one of the major pathogens of EV-associated diseases. The modified PCR primers and amplification conditions can effectively improve the reliability of test results.

Objective: To investigate the relationship between human bocavirus 2 (HBoV2) infection and acute diarrhea in children younger than 5 years of age in a case-control study. Methods: This was a prospective case-control study. During May 2016 to December 2016, fecal specimens were collected from children ≤5 years of age with acute diarrhea who visited the Affiliated Children's Hospital of Capital Institute of Pediatrics (case group), or from children ≤5 years of age without diarrhea from Longtan Community Medical Service Center, Beijing (control group). The case group (n=240) and the control group (n=240) were divided into 8 age subgroups: ≤1 month old, >1-3 months old, >3-6 months old, >6-12 months old,>1-2 years old,>2-3 years old,>3-4 years old and >4-5 years old, and there were 30 cases in each age subgroup. The specimens were tested for 7 types of diarrhea-associated viruses, especially for HBoV2 by real-time PCR method. The HBoV2 viral load was predicted according to the cycle threshold (Ct). Finally, t-test was used to compare the differences between groups. Results: In the case group (n=240), the positive rate of norovirus was 16.7% (40 cases); rotavirus, 10.8% (26 cases); HBoV2, 7.5% (18 cases); adenovirus, 7.1% (17 cases); astrovirus, 6.3% (15 cases); parachovirus, 3.8% (9 cases); and Aich virus, 0.4% (1 case). The positive rates of HBoV2 in case group (7.5%, 18 cases) and control group (5.0%, 12 cases) showed no significant difference (χ²=1.280, P=0.258), as well as in different age groups (all P>0.05) . However, the mean viral load of the HBoV2 in the case group (1×10⁹copies/L with cycle threshold (Ct) 25.8) was higher than that of control group (1×10⁵copies/L with Ct 33.8), showing a significant difference (t=0.597, P=0.000). Conclusions Norovirus and rotavirus are still the important viral pathogens in children with acute diarrhea. A higher load of HBoV2 may indicate a higher risk of acute diarrhea in children ≤5 years of age in Beijing.

AIM To optimize the ultrasound-microwave extraction for total flavonoids from Glycyrrhizae Radix et Rhizoma residue by response surface method.METHODS In addition to the index of extraction rate of total flavonoids for evaluation,the microwave power,extraction time,liquid-soild ratio and ethanol concentration were taken into consideration as influencing factors for the extraction optimization by response surface method on the basis of single factor test.RESULTS The optimal conditions,determined to be 125 W for microwave power,32 min for extraction time,28.4 ∶ 1 for liquid-solid ratio,79％ for ethanol concentration,and 300 W for extraction power,could bring forth a 2.59％ extraction rate of total flavonoids.CONCLUSION This stable and reliable method can be used for extracting total flavonoids from Glycyrrhizae Radix et Rhizoma residue.