Identifying EGFR mutations in lung adenocarcinoma by noninvasive imaging using radiomics features and random forest modeling.

OBJECTIVES: The tyrosine kinase inhibitor (TKI)-sensitive mutations of the epidermal growth factor receptor (EGFR) gene is essential in the treatment of lung adenocarcinoma. To overcome the difficulty of EGFR gene test in situations where surgery and biopsy samples are too risky to obtain, we tried a noninvasive imaging method using radiomics features and random forest models. METHODS: Five hundred three lung adenocarcinoma patients who received surgery-based treatment were included in this study. The diagnosis and EGFR gene test were based on resections. TKI-sensitive mutations were found in 60.8% of the patients. CT scans before any invasive operation were gathered and analyzed to extract quantitative radiomics features and build random forest classifiers to identify EGFR mutants from wild types. Clinical features (sex and smoking history) were added to the image-based model. The model was trained on a set of 345 patients and validated on an independent test group (n = 158) using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: The performance of the random forest model with 94 radiomics features reached an AUC of 0.802. Its AUC was further improved to 0.828 by adding sex and smoking history. The sensitivity and specificity are 60.6% and 85.1% at the best diagnostic decision point. CONCLUSION: Our results showed that radiomics could not only reflect the genetic differences among tumors but also have diagnostic value and the potential to be a diagnostic tool. KEY POINTS: • Radiomics provides a potential noninvasive method for the prediction of EGFR mutation status. • In situations where surgeries and biopsy are not available, CT image-based radiomics models could help to make treatment decisions. • The accuracy, sensitivity, and specificity still need to be improved before the image-based EGFR identifier could be used in clinics.

Immune persistence 17 to 20 years after primary vaccination with recombination hepatitis B vaccine (CHO) and the effect of booster dose vaccination.

BACKGROUND: To assess the immune persistence conferred by a Chinese hamster ovary (CHO)-derived hepatitis B vaccine (HepB) 17 to 20 years after primary immunization during early life. METHODS: Participants born between 1997 and 1999 who received a full course of primary vaccination with HepB (CHO) and who had no experience with booster vaccination were enrolled. Blood samples were required from each participant for measurement of hepatitis B surface antibody (anti-HBs), surface antigen and core antibody levels. For those who possessed an anti-HBs antibody < 10 mIU/mL, a single dose of HepB was administered, and 30 days later, serum specimens were collected to assess the booster effects. RESULTS: A total of 1352 participants were included in this study. Of these, 1007 (74.5%) participants could retain an anti-HBs antibody ≥10 mIU/mL, with a geometric mean concentration (GMC) of 57.4 mIU/mL. HBsAg was detected in six participants, resulting in a HBsAg carrier rate of 0.4% (6/1352). Of those participants with anti-HBs antibodies < 10 mIU/mL, after a challenge dose, 231 (93.1%) presented an anti-HBs antibody ≥10 mIU/mL, with a GMC of 368.7 mIU/mL. A significant increase in the anti-HBs positive rate (≥ 10 mIU/mL) after challenge was observed in participants with anti-HBs antibodies between 2.5 and 10 mIU/mL and participants boosted with HepB (CHO), rather than those with anti-HBs antibodies < 2.5 mIU/mL and those boosted with HepB (SC). CONCLUSION: Since satisfactory immune protection against HBV infection conferred by primary vaccination administered 17-20 years ago was demonstrated, there is currently no urgent need for booster immunization.

Burden and etiology of moderate and severe diarrhea in children less than 5 years of age living in north and south of China: Prospective, population-based surveillance.

BACKGROUND: Diarrhea remains the leading cause of childhood illness in China. Better understanding of burden and etiology of diarrheal diseases is important for development of effective prevention measures. METHODS: Population-based diarrhea surveillance was conducted in Sanjiang (southern China) year-round and Zhengding (northern China) in autumn/winter. Stool specimens were collected from children < 5 years of age experiencing diarrhea. The TaqMan Array Card (TAC), based on multiplex real-time PCR, was applied to detect multiple enteric microbial agents simultaneously. Results using these methods were compared to those derived from conventional PCR assays. RESULTS: During the study period, 6,380 children in Zhengding and 3,581 children in Sanjiang < 5 years of age participated. Three hundred and forty (31.2%) and 279 (22.9%) diarrhea episodes were identified as moderate-to-severe in the two counties, with incidence of 60.4 and 88.3 cases per 1,000 child-years in Zhengding and Sanjiang, respectively. The five most frequently detected bacterial and viral agents in Sanjiang were adenovirus, enterovirus, enteroaggregative Escherichia coli (EAEC), rotavirus, and sapovirus all the year round, while the most common viral agents in Zhengding were rotavirus, followed by astrovirus and adenovirus during the cool season. Compared to conventional PCR assay, the average incremental detection via the TAC method was twofold. CONCLUSION: Our study demonstrated high diversity and prevalence of multiple major bacterial and viral agents, including rotavirus and calicivirus, among children in China. Further studies are needed to define the public health significance of neglected but frequently detected pathogens such as EAEC, enterotoxigenic E. coli, Campylobacter, adenovirus, and enterovirus.

Genetic susceptibility to rotavirus infection in Chinese children: a population-based case-control study.

Rotaviruses (RVs) are the leading cause of acute gastroenteritis in children, while histo-blood group antigens (HBGAs) are believed to be host attachment and susceptibility factors of RVs. A large case-control study nested in a population-based diarrhea surveillance targeting children <5 y of age was performed in rural Hebei province, north China. Saliva and serum samples were collected from all participants to determine HBGA phenotyping, FUT2 mutations, and RV IgG antibody titers. A logistic model was employed to assess the association between host HBGA secretor status and risk of RV infection. Among 235 RV cases and 680 non-diarrhea controls studied, 82.4% of participants were IgG positive by an average age of 77 months. Out of the 235 RV cases, 216 (91.9%) were secretors, whereas the secretor rate was 76.3% in the non-diarrhea controls, resulted in an adjusted OR of 3.0 (95%CI: 1.9-4.7, P < .0001) between the two groups. Our population-based case-control study indicated a strong association between host HBGA secretor status and risk of RV infection in Chinese children. The high prevalence of Lewis-positive secretor status strongly suggests that Chinese children may be genetically susceptible to current co-circulating RV strains, and thus, a universal childhood immunization program against RV disease should be successful in China.

Long-term protection at 20-31 years after primary vaccination with plasma-derived hepatitis B vaccine in a Chinese rural community.

Background: To assess the long-term protection conferred by plasma-derived hepatitis B vaccine at 20-31y after primary immunization during infancy in Chinese rural community.Method: Participants born between 1986 and 1996, who received a full course of primary vaccination with plasma-derived hepatitis B vaccine and had no experience with booster vaccination were enrolled. An epidemiological investigation was performed, and blood samples were collected to detect hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc). The positive rate of HBsAg, anti-HBs, and anti-HBc were calculated to evaluate the long-term protection of the plasma-derived hepatitis B vaccine.Results: A total of 949 participants were enrolled in the final analysis. Six subjects were detected to be HBsAg-positive, resulting in a HBsAg carrier rate of 0.63% (6/949). A total of 468 (52.41%) participants maintained a level of anti-HBs antibody ≥10 mIU/mL, with a GMC of 112.20 mIU/mL (95%CI: 97.72 ~ 128.82 mIU/mL). A significant downtrend was observed in the anti-HBs positive rate (P < .001). The average anti-HBc positive rate was 5.90% (56/949), increased with prolongation of immunization (P < .001).Conclusions: The plasma-derived hepatitis B vaccine maintained satisfactory protection at 20-31 y after primary immunization. These results indicate that a booster dose is not necessary. Further studies on the immune memory induced by the plasma-derived hepatitis B vaccine are needed.

Immune response to different types of hepatitis B vaccine booster doses 2-32 years after the primary immunization schedule and its influencing factors.

OBJECTIVE: To assess the immune effect of different types of hepatitis B vaccine (HepB) booster doses 2-32 years after primary immunization, explore the influencing factors, and offer guidance regarding the necessity and timing of boosters. METHODS: In total, 1163 participants who were born from 1986 to 2015, received the HepB full-course primary vaccination, were hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) negative, and had hepatitis B surface antibody (anti-HBs) <10 mIU/mL were enrolled. Individuals were randomly divided into two groups and received a booster dose of HepB. Venous blood samples were collected 30 days later and tested for anti-HBs. RESULTS: In total, 595 and 568 individuals received a single dose of HepB (CHO) and HepB (SC), respectively. Venous blood samples were obtained from 1079 vaccinees (CHO: 554, SC: 525). The seroconversion rates were 93.68% (519/554) and 86.67% (455/525) (p < 0.05), with geometric mean concentrations (GMCs) of 426.58 mIU/ml and 223.8 mIU/ml, respectively. This result indicated that BMI, smoking status, vaccine types of booster and prebooster anti-HBs concentration significantly influenced anti-HBs levels. Only BMI, prebooster anti-HBs concentrations and booster types were different between the anti-HBs positive and negative groups. CONCLUSIONS: Participants boostered with HepB (CHO) had a relatively higher seroconversion rate than those boostered with HepB (SC). The high seroconversion rates in the two groups suggested that the subjects remained protected despite low circulating antibodies, so there is currently no urgent need for booster immunization. Factors including BMI ≥ 25 and prebooster anti-HBs concentration <2.5 mIU/mL, which contributed to lower responses to a booster dose, might indicate a greater risk of breakthrough infection.

Burden of viral gastroenteritis in children living in rural China: Population-based surveillance.

BACKGROUND: Despite the considerable disease burden caused by the disease, rotavirus vaccine has not been introduced into routine national immunization schedule, and norovirus vaccines are being developed without a comprehensive understanding of gastroenteritis epidemiology. To bridge this knowledge gap, we investigated the disease burden of viral gastroenteritis in rural China. METHODS: Between October 2011 and December 2013, population-based surveillance was conducted in Zhengding and Sanjiang counties in China. Stool samples were collected from children <5 years of age with diarrhea. All specimens were tested for rotaviruses, noroviruses, sapoviruses, enteric adenoviruses, and astroviruses. RESULTS: The most common pathogen causing diarrhea was rotavirus (54.7 vs 45.6 cases/1,000 children/year in Zhengding and Sanjiang, respectively), followed by norovirus (28.4 vs 19.3 cases/1,000 children/year in Zhengding and Sanjiang, respectively). The highest incidence of these viruses was observed in children 6-18 months of age. Among the 5 viral pathogens, rotaviruses caused the most severe illness, followed by noroviruses. CONCLUSION: Rotavirus and norovirus are the 2 most important viral pathogens causing childhood diarrhea in both northern and southern China; they should be the major targets for viral gastroenteritis prevention strategies among children in China.

Potential cost-effectiveness of a rotavirus immunization program in rural China.

BACKGROUND: To assess the incidence and economic burden of rotavirus diarrhea and the potential cost-effectiveness of a rotavirus immunization program in rural Zhengding County in Hebei Province, China. METHODS: Population-based surveillance was conducted during the peak season for diarrhea among children who were <5 years of age in Zhengding County from 14 October 2004 through 19 January 2005. The cost of illness was measured from the perspectives of both patient and society. A decision-analytic model was applied to the cost-effectiveness analysis using real data derived from surveillance and from a cost-of-illness study. RESULTS: During the surveillance period, 500 episodes of diarrhea were registered. Of these 500 episodes, 125 (25%) occurred in patients who were positive for rotavirus. Of these 125 episodes, 63 (50%) occurred in patients who were hospitalized. The overall incidence rate of rotavirus infection was 61.4 cases per 1000 children per year during the 14-week epidemic season. For a Chinese cohort of 5000 newborns, a universal rotavirus immunization program would prevent 1764 cases of rotavirus diarrhea, averting 882 hospitalizations of patients

Immune memory at 17-years of follow-up of a single dose of live attenuated hepatitis A vaccine.

BACKGROUND: In recent years, hepatitis A virus (HAV) infection has declined considerably in China, associated with wide deployment of HAV vaccines and improvement in socio-economic indicators. Towards the elimination of HA in the country, we assessed the duration and characteristics of immunity conferred by the widely used, locally manufactured HAV vaccine. METHODS: This is a longitudinal cohort study that followed recipients of a live attenuated HAV vaccine 17 years after the initial administration. Blood samples were collected from participants pre- and two-week post-booster HAV vaccine dose. Serum anti-HAV antibody was measured by ELISA method. Memory B and T cells were determined by ELISPOT and Flow Cytometry assays, respectively. RESULTS: A robust anamnestic response was observed two-week post-challenge. Both HAV-specific memory B cell and T cells remained, and responded quickly when re-encountering HAV. The magnitude of recall responses was present, regardless of the status of the serum anti-HAV antibody pre-booster. CONCLUSIONS: We demonstrated long-term immunity from the live attenuated HAV vaccine, including antibody persistence and immunological memory. Considering the conditions that make elimination of infectious diseases feasible, following polio, hepatitis A could be targeted for elimination in China.

Variation analysis of norovirus among children with diarrhea in rural Hebei Province, north of China.

To understand the distribution of genotyping, as well as evolution of norovirus circulating among children<5yrs., a population-based diarrhea surveillance targeted children<5yrs. was conducted in rural Zhengding County, Hebei Province, China between October 2011 and March 2012. RT-PCR was used to amplify the capsid-encoding region of GI and GII norovirus to identify norovirus infection. All PCR products were sequenced and analyzed for genotyping and constructing phylogenetic tree. Dynamic distribution network was constructed by TempNet to illustrate the genetic relationships at two different time points. Bayesian evolutionary inference techniques were applied by BEAST software to study the norovirus evolution rate. During the 6-month surveillance period, 1091 episodes of diarrhea were reported from 5633 children under 5years of age lived in catchment area. 115 of 1091 stool specimens were detected as norovirus positive (10.54%). Five genotypes based on capsid gene sequences were identified, including GII.2 (11), GII.3 (52), GII.4 (47), GII.6 (4) and GII.7 (1). An identical haplotype of GII.4 circulated between 2006 and 2011 in Hebei Province. A mean rate of 6.29×10-2 nucleotide substitutions/site/year (s/s/y) was obtained for GII.3 viruses in Hebei, while the GII.4 viruses evolved at a mean rate of 3.67×10-2s/s/y. In conclusions, GII.3 (45.22%) and GII. 4(40.87%) are the predominant strain in Hebei Province in the winter season of 2011 and 2012. Different from the current consensus, our study shows that GII.3 noroviruses in Hebei Province evolved at a faster rate than GII.4 viruses.

Occurrence of shigellosis in the young and elderly in rural China: results of a 12-month population-based surveillance study.

In 2002, population- and treatment center-based surveillance was used to study the disease burden of shigellosis in rural Hebei Province in the People's Republic of China. A total of 10,105 children with diarrhea or dysentery were enrolled. Infants were treated most frequently for diarrhea (1,388/1,000/year) followed by children < or = 5 years old (618/1,000/year). Shigellosis was treated most often in children 3-4 years old (32/1,000/year) and people > 60 years of age (7/1,000/year). Fifty-six percent (184 of 331) Shigella isolates were detected in patients who had non-bloody diarrhea. Shigella flexneri was identified in 93% of 306 isolates. The most common S. flexneri serotypes were 1a (34%), X (33%), and 2a (28%). More than 90% of the Shigella isolates were resistant to cotrimoxazole and nalidixic acid, but remained susceptible to ciprofloxacin, norfloxacin, and gentamicin. Widespread resistance to antibiotics adds urgency to the development and use of vaccines to control shigellosis.

Effectiveness of the live attenuated rotavirus vaccine produced by a domestic manufacturer in China studied using a population-based case-control design.

A universal rotavirus (RV) immunization program is a potentially cost-effective measure for preventing RV infection in China. However, the efficacy of the only licensed RV vaccine (Lanzhou lamb rotavirus vaccine, LLR), which is made by a domestic manufacturer, has not been proven by a properly designed clinical trial. In October 2011 to March 2012, to measure the potential protection provided by LLR, a case-control study nested in a population-based active diarrhea surveillance study of children <5 years of age was conducted in rural Zhengding county. During the study period, 308 episodes of diarrhea were identified as being caused by RV infection, resulting in an incidence rate of 48.0/1000 people/year. The predominant RV serotype was G3 (61.5%), followed by G1 (15.2%), and G9 (6.5%). Overall, a protection of 35.0% (95% confidence interval (CI), 13.0%-52.0%) was identified, and higher protection was found among moderate RV gastroenteritis cases caused by the serotype G3 (52.0% 95% CI: 2.0%-76.1%). A concurrently conducted case-control study comparing non-RV viral diarrheal cases with non-diarrheal controls in the same population found that the RV vaccine offered no protection against non-RV diarrhea. Even under a less ideal immunization schedule, the oral LLR conferred a certain level of protection against RV gastroenteritis. However, further studies are needed to understand the full characteristics of the LLR, including its efficacy when administered following the optimal regimen, the potential risk of inducing intussusception, and the direct and indirect protective effects of LLR.

Waning of anti-HAV immunity in Shijiazhuang prefecture, Hebei province, China: a comparison of seroprevalence between 1992 and 2011.

OBJECTIVE: To study the epidemiological patterns of hepatitis A, and immunity of entire population in Shijiazhuang prefecture, Hebei province, a former hyper-endemic area in north China. METHODS: Cross-sectional, seroprevalence surveys with two-stage cluster sampling were conducted among population older than 2-year between 1992 and 2011. During the 2011 serological survey, blood samples from infants <18 months without hepatitis A immunization history were also collected to determine maternal anti-HAV antibody. Serum samples were tested for anti-HAV antibody by domestic reagent or Abbott reagent. Viral hepatitis incidence rates and gross domestic product data were derived from local governmental statistics. RESULTS: Concomitant with the reduction of reported hepatitis A cases between 1992 and 1996 was a significant decline of HAV infections. The average prevalence decreased from 93.6% to 41.9%, and the average age at new infection was postponed from infancy to adolescence. This was attributed to improved socio-economic conditions. With intensive vaccination, a return of new seroconversion rate and seroprevalence was observed. A well fitted exponential regression equation (R(2)=0.96, p<0.0001) modeled that the maternal antibody would wane to <20 mIU/mL at 13 months. CONCLUSION: Benefiting from the booming economy, rapid improvement in sanitation, safe water supply, and implementation of hepatitis A vaccines, the epidemiological pattern of hepatitis A moved from high to intermediate endemicity in Shijiazhuang. Policy makers should be aware of the waning of immunity in entire population, and adapt immunization strategy timely, to ensure a lifelong protection against hepatitis A virus.

Long-term efficacy of 10-12 years after being immunized with Chinese hamster ovary cell derived hepatitis B vaccine in Chinese Rural Communities.

OBJECTIVE: To evaluate the long-term efficacy of Chinese hamster ovary (CHO) cell derived hepatitis B vaccine in country community in China. METHODS: A cross-sectional investigation was carried out. Children who were born between 1997 and 1999 and vaccinated with the three doses of CHO-derived hepatitis B vaccine were selected as study objects. Their serum samples were taken to test for hepatitis B virus (HBV) markers, and the results were compared to that before vaccination. In addition, for HBsAg positive children, their mothers were visited. RESULTS: 1254 Children were enrolled in the study. The prevalence of HBsAg was 0.24% and the vaccine efficacy was 97.0%, similar to that of yeast derived hepatitis vaccines. Among 3 mothers of HBsAg positive children, 2 were HBsAg positive, indicating maternal HBV transmissions. CONCLUSION: The long-term efficacy of the CHO-derived hepatitis B vaccine is good and after vaccination maternal transmission is the most important route of spreading HBV.

Effectiveness of a Chinese hamster ovary cell derived hepatitis B vaccine in Chinese rural communities.

OBJECTIVE: To evaluate the effectiveness of a Chinese hamster ovary cell derived hepatitis B vaccine in a country community in Hebei Province, PR China. METHOD: A cross-sectional investigation was carried out in 4 of 7 randomly selected country communities in Zhengding County in 2005. All of the children who were born between 1997 and 1999 were selected as study objects. Their serum samples were taken to test for HBV markers, and HBsAg prevalence was compared to that of the same age group before hepatitis B vaccination in 1983. In addition, for HBsAg positive children, their mothers were visited and tested for serum HBV markers, in order to distinguish maternal HBV transmissions. RESULTS: Among the 2205 children of the selected birth cohort, 1696 (76.9%) were visited. The prevalence of HBsAg was 0.53%, and by comparing to that of before hepatitis B vaccination, the effectiveness was 95.3%, similar to that of yeast derived hepatitis B vaccines. Among 7 mothers of HBsAg positive children, 5 were HBsAg positive, indicating maternal HBV transmissions; and although one mother was HBsAg negative, her kid was not vaccinated, which indicates a horizontal transmission. As for the other kid, he was adopted and the HBV infection status of his birth mother was unknown. CONCLUSION: The effectiveness of the CHO derived hepatitis B vaccine is comparable to yeast derived ones, and after the hepatitis B vaccination maternal transmission is the most important route of spreading HBV.

Influenza and bacterial pathogen coinfections in the 20th century.

To help understand the potential impact of bacterial coinfection during pandemic influenza periods, we undertook a far-reaching review of the existing literature to gain insights into the interaction of influenza and bacterial pathogens. Reports published between 1950 and 2006 were identified from scientific citation databases using standardized search terms. Study outcomes related to coinfection were subjected to a pooled analysis. Coinfection with influenza and bacterial pathogens occurred more frequently in pandemic compared with seasonal influenza periods. The most common bacterial coinfections with influenza virus were due to S. pneumoniae, H. influenzae, Staphylococcus spp., and Streptococcus spp. Of these, S. pneumoniae was the most common cause of bacterial coinfection with influenza and accounted for 40.8% and 16.6% of bacterial coinfections during pandemic and seasonal periods, respectively. These results suggest that bacterial pathogens will play a key role in many countries, as the H1N1(A) influenza pandemic moves forward. Given the role of bacterial coinfections during influenza epidemics and pandemics, the conduct of well-designed field evaluations of public health measures to reduce the burden of these common bacterial pathogens and influenza in at-risk populations is warranted.

Surveillance of shigellosis by real-time PCR suggests underestimation of shigellosis prevalence by culture-based methods in a population of rural China.

INTRODUCTION: Shigellosis is a leading public health issue in China, especially in Children under 5 years of age. The disease burden of shigellosis is usually underestimated by conventional culture. In this study, real-time PCR was applied to detect Shigella infection in parallel with routine culture, to investigate the true burden of disease caused by Shigella spp. METHODS: Rectal swab specimens of 39 Shigella culture positive and 298 Shigella culture negative patients from a population-based surveillance study were selected randomly. Real-time PCR targeting the invasion plasmid antigen H gene sequence (ipaH) was used to detect DNA sequences characteristic for Shigella spp. RESULTS: ipaH were detected in 174 of 298 (58%) randomly selected Shigella culture negative specimens and in 38 of 39 (97%) Shigella culture positive specimens (p < 0.001). Among 10 variables, culture results was the strongest predictive factor (OR = 15.5; 95% CI: 2.0-119.0), followed by a clinical presentation of diarrhea with fever (OR = 2.8; 95% CI: 1.2-6.2), epidemic season (OR = 2.4; 95% CI: 1.4-4.3), and female gender (OR = 1.8; 95% CI: 1.1-3.0). CONCLUSION: The high detection rate of ipaH in culture negative specimens through use of real-time PCR suggests that earlier estimates of shigellosis burden measured by conventional culture may have underestimated the true disease burden.

[Establishment of hepatitis B virus marker panels].

OBJECTIVE: To establish HBV marker panels. METHODS: 155 blood plasma specimens were selected and each was detected twice for 5 HBV markers with MEIA kits made by Abbott. Any plasma that had 2 positive or negative results were enrolled in the HBV marker panels and others were excluded. RESULTS: 153 plasma were enrolled in the HBsAg panel and 154 were enrolled in anti-HBs, anti-HBc and anti-HBe panels respectively. Panel of HBeAg was not established because that there were only 4 positives. CONCLUSION: HBV marker panels can be established by screening enough blood plasma specimens with high accurate kits for more than one time. The panels should be used in a limited extension to avoid unnecessary mistakes.

[Evaluation of 5 kinds of China-made enzyme immunoassay kits for antibody to hepatitis B virus surface antigen detection].

OBJECTIVE: To Screen an EIA kit that fits best for using in serological detection of anti-HBs in the national investigation of hepatitis B virus infection. METHODS: Top 5 kinds of kits on the best seller list of China-made anti-HBs EIA detection kits were selected and each was detected the anti-HBs panel(44 positive and 108 negative) 5 times. The s/n ratio of each test was recorded and transformed by log(s/n+1). ICC and CV, the reliability indices and AUC, pAUC and Se(FPR=e), the validity indices were calculated and compared between each kit. RESULTS: The indices of ICC and CV of the 5 kinds of kits arranged in the same order of D, E, B, C and A, from the best to the worst and the differences between them were significantly important (Bootstrap method, P < 0.05), except for between E and B in the index of CV; the AUCs ranged from 0.980 to 0.993 and pAUCs did not differ with each other, except with kit A, the lowest one. Kit E had the highest sensitivity which was higher than kits B, C and D when the specificity was fixed at 0.97, and the later kits were higher than kit A(Bootstrap method, P < 0.05). CONCLUSION: All the 5 kits are excellent and have synthetically considered the reliability and validity indicators and its function, kit D is the best.