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In clinical practice, sera creatinine level is regarded as a crucial biomarker for the diagnosis, staging and monitoring of kidney disease. An amperometric biosensor is rapid, accurate, and cost-effective, with a portability and a simple operation. Herein, we report for the firsttime a disposable, printed amperometric biosensor for the clinical evaluation of creatinine in renal function detection. The sensor is constructed based on Prussian blue/carbon-graphite paste as the working electrode and the immobilization of creatinine amidohydrolase, creatine amidinohydrolase and sarcosine oxidase. The creatinine biosensor shows a linear detection range from 0.05 to 1.4 mM with a detection time of about 3 min. In addition, the sensor shows a high stability that can maintain above 86% of the initial activity after being stored for over 4 months. Moreover, the sensor shows almost the same results as those with the Jaffe method for measuring the real blood samples. We anticipate that the creatinine biosensor could be widely used in the medical and healthcare areas, especially for at-home testing and onsite medical examinations.

BACKGROUND Early detection of hepatocellular carcinoma (HCC) among hepatitis B virus (HBV)-infected patients remains a challenge, especially in China. We sought to create an online calculator of serum biomarkers to detect HCC among patients with chronic hepatitis B (CHB). METHODS Participants with HBV-HCC, CHB, HBV-related liver cirrhosis (HBV-LC), benign hepatic tumors, and healthy controls (HCs) were recruited at 11 Chinese hospitals. Potential serum HCC biomarkers, protein induced by vitamin K absence or antagonist-II (PIVKA-II), α-fetoprotein (AFP), lens culinaris agglutinin A-reactive fraction of AFP (AFP-L3) and α-L-fucosidase (AFU) were evaluated in the pilot cohort. The calculator was built in the training cohort via logistic regression model and validated in the validation cohort. RESULTS In the pilot study, PIVKA-II and AFP showed better diagnostic sensitivity and specificity compared with AFP-L3 and AFU and were chosen for further study. A combination of PIVKA-II and AFP demonstrated better diagnostic accuracy in differentiating patients with HBV-HCC from patients with CHB or HBV-LC than AFP or PIVKA-II alone [area under the curve (AUC), 0.922 (95% CI, 0.908–0.935), sensitivity 88.3% and specificity 85.1% for the training cohort; 0.902 (95% CI, 0.875–0.929), 87.8%, and 81.0%, respectively, for the validation cohort]. The nomogram including AFP, PIVKA-II, age, and sex performed well in predicting HBV-HCC with good calibration and discrimination [AUC, 0.941 (95% CI, 0.929–0.952)] and was validated in the validation cohort [AUC, 0.931 (95% CI, 0.909–0.953)]. CONCLUSIONS Our results demonstrated that a web-based calculator including age, sex, AFP, and PIVKA-II accurately predicted the presence of HCC in patients with CHB. ClinicalTrials.gov Identifier NCT03047603

Aim: To evaluate the diagnostic performance of serum AFU for early stage hepatocellular carcinoma (HCC). Methods: Concentration of AFU and AFP were measured in 512 patients. The performance was compared for AFU and AFP alone or in combination. Results: The area under the curve (AUC) for AFU was 0.68, with a sensitivity of 56.1% and specificity of 69.2% at the cut-off value of 24 U/l; whereas the AUC for AFP was 0.83, with a sensitivity of 58.2% and specificity of 85.2% at cut-off value of 20 ng/ml. The AUC of AFU alone or the combination with AFP were lower than that of AFP alone. Conclusion: AFU is a suboptimal biomarker for early detection of HCC.

Background To avoid false negative results, hepatitis B surface antigen (HBsAg) assays need to detect samples with mutations in the immunodominant ‘a’ determinant region, which vary by ethnographic region. Objective We evaluated the prevalence and type of HBsAg mutations in a hepatitis B virus (HBV)-infected East- and Southeast Asian population, and the diagnostic performance of the Elecsys® HBsAg II Qualitative assay. Study design We analyzed 898 samples from patients with HBV infection from four sites (China [Beijing and Guangzhou], Korea and Vietnam). HBsAg mutations were detected and sequenced using highly sensitive ultra-deep sequencing and compared between the first (amino acids 124–137) and second (amino acids 139–147) loops of the ‘a’ determinant region using the Elecsys® HBsAg II Qualitative assay. Results Overall, 237 distinct amino acid mutations in the major hydrophilic region were identified; mutations were present in 660 of 898 HBV-infected patient samples (73.5%). Within the pool of 237 distinct mutations, the majority of the amino acid mutations were found in HBV genotype C (64.8%). We identified 25 previously unknown distinct mutations, mostly prevalent in genotype C-infected Korean patients (n = 18) followed by Chinese (n = 12) patients. All 898 samples were correctly identified by the Elecsys® HBsAg II Qualitative assay. Conclusions We observed 237 distinct (including 25 novel) mutations, demonstrating the complexity of HBsAg variants in HBV-infected East- and Southeast Asian patients. The Elecsys® HBsAg II Qualitative assay can reliably detect HBV-positive samples and is suitable for routine diagnostic use in East and Southeast Asia.

This study aimed to build a valid diagnostic nomogram for assessing the cancer risk of the pulmonary lesions identified by chest CT.A total of 691 patients with pulmonary lesions were recruited from three centers in China. The cut-off value for each tumor marker was confirmed by minimum P value method with 1000 bootstrap replications. The nomogram was based on the predictive factors identified by univariate and multivariate analysis. The predictive performance of the nomogram was measured by concordance index and calibrated with 1000 bootstrap samples to decrease the overfit bias. We also evaluated the net benefit of the nomogram via decision curve analysis. Finally, the nomogram was validated externally using a separate cohort of 305 patients enrolled from two additional institutions.The cut-off for CEA, SCC, CYFRA21-1, pro-GRP, and HE4 was 4.8 ng/mL, 1.66 ng/mL, 1.83 ng/mL, 56.55 pg/mL, and 63.24Lpmol/L, respectively. Multivariate logistic regression model (LRM) identified tumor size, CEA, SCC, CYFRA21-1, pro-GRP, and HE4 as independent risk factors for lung cancer. The nomogram based on LRM coefficients showed concordance index of 0.901 (95% CI: 0.842-0.960; P 0.001) for lung cancer in the training set and 0.713 (95% CI: 0.599-0.827; P 0.001) in the validation set. Decision curve analysis reported a net benefit of 87.6% at 80% threshold probability superior to the baseline model.Our diagnostic nomogram provides a useful tool for assessing the cancer risk of pulmonary lesions identified in CT screening test.

Objectives Alpha-fetoprotein (AFP) has been widely used in clinical practice for decades. However, large-scale survey of serum reference interval for ARCHITECT AFP is still absent in Chinese population. This study aimed to measure serum AFP levels in healthy Chinese Han subjects, which is a sub-analysis of an ongoing prospective, cross-sectional, multi-center study ( ClinicalTrials.gov Identifier: NCT03047603 ). Methods This analysis included a total of 530 participants (41.43 ± 12.14 years of age on average, 48.49% males), enrolled from 5 regional centers. Serum AFP level was measured by ARCHITECT immunoassay. Statistical analysis was performed using SAS 9.4 and R software. Results AFP distribution did not show significant correlation with age or sex. The overall median and interquartile range of AFP was 2.87 (2.09, 3.83) ng/mL. AFP level did not show a trend of increasing with age. The new reference interval was 2.0–7.07 ng/mL (LOQ– 97.5th percentiles). Conclusions The reference interval for ARCHITECT AFP is updated with the data of adequate number of healthy Han adults. This new reference interval is more practical and applicable in Chinese adults.

Background China is undergoing a rapid growth in the human immunodeficiency virus (HIV) epidemic involving men who have sex with men (MSM). Reports about their health-related quality of life (HRQOL) are scarce. This study aimed to assess the HRQOL and factors influencing HIV-positive MSM in a city in the northeast of China. Material/Methods A cross-sectional study was conducted in Harbin city (Heilongjiang, China). HIV-positive MSM (n=125) were interviewed using the WHOQOL-HIV-BRIEF scale, the Berger HIV Stigma Scale, and other HIV-related questionnaires from June to August 2013. Results Among the 6 dimensions of the HRQOL, HIV-related stigma was negatively associated with psychological (r=−0.316, P=0.0003) and spirituality domains (r=−0.324, P=0.0002). Physician support was positively associated with independence domain (r=0.393, P350 (OR=0.033, 95%CI: 0.005–0.208, P=0.001) were independent protective factors in MSM receiving HAART. Hostile mentality (OR=0.936, 95%CI: 0.906–0.967, P

This study aimed to explore the efficacy of propofol to treat malignant pheochromocytoma (PCC) in vitro and in vivo. In vitro, PC12 cells were treated with different concentrations of propofol (0, 1, 5, and 10 μg/mL) for specific times followed by a MTT assay to detect cell proliferation. Transwell assays were performed to assess the function of propofol on the migration and invasion of PC12 cells, and flow cytometry to analyze cell apoptosis and cell cycle progression. Quantitative real-time polymerase chain reaction was carried out to analyze the expression level of mRNA (Bcl-2, Bax, and CyclinE). The levels of Bcl-2, Bax, CyclinE, FOXO1, FOXO3, Bim, procaspase-3, and active caspase-3 were determined by western blotting. In vivo, the effects of propofol on PCC tumor growth were detected by transplanted mouse model. Transferase dUTP nick-end labeling was performed to detect tissue cell apoptosis. The results indicated that propofol inhibited PC12 cell proliferation, prevented cell migration and invasion, and induced the apoptosis of PC12 cells in a dose- and time-dependent manner. Propofol treatment increased the expression of Bax and decreased that of Bcl-2. In addition, propofol significantly induced the G1/S phase arrest in PC12 cells, and the expression of Cyclin E was reduced. Moreover, the levels of FOXO1, FOXO3, Bim, procaspase-3, and active caspase-3 were enhanced by propofol treatment. In vivo, propofol treatment significantly reduced the PCC tumor growth and induced tissue cell apoptosis. In conclusion, propofol has potent anti-PCC activity in vitro and in vivo, and is a potential small-molecule drug for treating malignant PCC.

Protein induced by vitamin K absence or antagonist-II (PIVKA-II) has been widely used as a biomarker for liver cancer diagnosis in Japan for decades. However, the reference intervals for serum ARCHITECT PIVKA-II have not been established in the Chinese population. Thus, this study aimed to measure serum PIVKA-II levels in healthy Chinese subjects.This is a sub-analysis from the prospective, cross-sectional and multicenter study (ClinicalTrials.gov Identifier: NCT03047603). A total of 892 healthy participants (777 Han and 115 Uygur) with complete health checkup results were recruited from 7 regional centers in China. Serum PIVKA-II level was measured by ARCHITECT immunoassay. All 95% reference ranges were estimated by nonparametric method.The distribution of PIVKA-II values showed significant difference with ethnicity and sex, but not age. The 95% reference range of PIVKA-II was 13.62-40.38 mAU/ml in Han Chinese subjects and 15.16-53.74 mAU/ml in Uygur subjects. PIVKA-II level was significantly higher in males than in females (P 0.001). The 95% reference range of PIVKA-II was 15.39-42.01 mAU/ml in Han males while 11.96-39.13 mAU/ml in Han females.The reference interval of serum PIVKA-II on the Architect platform was established in healthy Chinese adults. This will be valuable for future clinical and laboratory studies performed using the Architect analyzer. Different ethnic backgrounds and analytical methods underline the need for redefining the reference interval of analytes such as PIVKA-II, in central laboratories in different countries.

Background More than 50% of hepatocellular carcinoma (HCC) are caused by hepatitis B virus (HBV) infection and almost one third of carriers of hepatitis B virus (HBV) world-wide are in China. Early detection of HCC in HBV-infected patients remains a challenge. Methods Consecutive participants with HBV-related HCC, chronic hepatitis B (CHB), liver cirrhosis with HBV infection (HBV-LC), benign hepatic tumors and healthy controls at 11 hospitals in China from June 2016 to April 2017 were recruited to form a training cohort. Participants from the same hospitals from May 2017 to September 2017 were recruited to form a validation cohort. All HCCs were diagnosed by ultrasound, characteristic radiologic features on CT/MRI, and confirmed by histopathological examination from biopsy or surgically resected specimens. Findings 908 of 2207 (41.1%) participants in the training cohort and 289 of 730 (39.6%) participants in the validation cohort were diagnosed to have HBV-related HCC. The serum levels of PIVKA-II and AFP were significantly higher in patients with HBV-related HCC than in those with CHB, HBV-LC or in controls (P

Backgroud Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are common infectious agents worldwide and the primary infection of HSV remains a major problem in the pregnant women in China nowadays. At present, typing detection of HSV is mainly based on ELISA in China. Methods In this study, we evaluated the performance of a newly introduced chemiluminescent immunoassay assay (CLIA) for the determination of serum HSV-1 and HSV-2 immunoglobulin G (IgG) antibodies. Results The functional sensitivity of detecting HSV-1 and HSV-2 IgG were 0.7 Index and 0.6 Index, respectively. The repeatability and the total imprecision coefficient of variations were both below 10%, and the recoveries of these assays ranged from 90% to 110%. High concentration of hemoglobin, lipids, and bilirubin in samples did not affect the results. The infective rates of HSV-1 and HSV-2 were 919 (87.5%) and 169 (16.1%), respectively. HSV-1 seroprevalence was significantly higher than that of HSV-2 (P < 0.001). Conclusion CLIA is an excellent method for HSV-1 and HSV-2 IgG measurement and can be used as a routine screening test. The infective rate of HSV was pretty high among women before pregnancy or in the period of pregnancy in Beijing.

Background To investigate the diagnostic performance of alpha-fetoprotein (AFP) and neutrophil-to-lymphocyte ratio (NLR) as well as their combinations with other markers. Methods Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), AFP and levels as well as the numbers of neutrophils and lymphocytes of all enrolled patients were collected. The NLR was calculated by dividing the number of neutrophils by the number of lymphocytes. Receiver operating characteristic (ROC) curve analysis was conducted to determine the ability of each marker and combination of markers to distinguish HCC and liver disease patients. Results In total, 545 patients were included in this study. The area under the ROC curve (AUC) values for AFP, ALT, AST, and NLR were 0.775 (0.738–0.810), 0.504 (0.461–0.547), 0.660 (0.618–0.699), and 0.738 (0.699–0.774) with optimal cut-off values of 24.6 ng/mL, 111 IU/mL, 27 IU/mL, and 2.979, respectively. Of the four biomarkers, AFP and NLR showed comparable specificity (0.881 and 0.858) and sensitivity (0.561 and 0.539). The combination of AFP and NLR showed the highest AUC (0.769) with a significantly higher sensitivity (0.767) and a lower specificity (0.773) compared to AFP or NLR alone, and it had the highest sum of sensitivity and specificity (1.54) among all combinations. In patients with AFP

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Early diagnosis improves the prognosis. Protein induced by vitamin K antagonist-II (PIVKA-II) is an effective serum biomarker for HCC diagnosis and prognosis. Combined with another serum biomarker α-fetoprotein (AFP), the sensitivity and specificity of HCC diagnosis can be improved to a maximum of 94 and 98.5 %, respectively. PIVKA-II alone or in combination with AFP and/or AFP-L3 was effective in predicting the treatment response and clinical outcome of curative hepatic resection, chemotherapy, targeted therapy, radiotherapy, and liver transplantation. Japanese clinical guidelines recommend the combined use of PIVKA-II and AFP for the diagnosis of HCC, management of high-risk population, and prognosis of anticancer treatment. Further, PIVKA-II as a functional target promoted HCC cell proliferation, invasion, and metastasis by activating c-Met and other signal transduction pathways. Inhibition of PIVKA-II may provide a selective and effective therapy for HCC.

Serum separator tubes were introduced 35 years ago and were widely used in the clinical laboratory in China for routine collection of blood because of providing a closed system that allowed for collection, transport, processing, sampling, and storage of specimens. This type of tubes facilitated rapid separation of serum from cellular constituents of blood and also prevented hemolysis upon prolonged storage. However, there were some limitations associated with gel tubes (i.e., gel and analyte stability). In order to circumvent these problems, BD released a new serum separator tube containing a new gel (BD SST(™) II Plus). We investigated theperformance of BD SST(™) II Plus tubes for tumor marker tests using BD Serum Glass tubes as controls. Equivalence between the BD SST(™) II Plus and BD Serum Glass tubes was demonstrated for all analytes at initial time. Also, all analytes remained stable when stored in BD SST(™) II Plus tubes up to 72 hr. Concentration of neuron‐specific enolase tended to increase with preservation time up to 72 hr in BD Serum Glass tubes. We conclude that BD SST(™) II Plus was suitable for collection of blood and storage of serum for tumor marker tests. J. Clin. Lab. Anal. 24:418–421, 2010. © 2010 Wiley‐Liss, Inc.

BACKGROUD: Herpes simplex virus types 1 and 2 (HSV‐1 and HSV‐2) are common infectious agents worldwide and the primary infection of HSV remains a major problem in the pregnant women in China nowadays. At present, typing detection of HSV is mainly based on ELISA in China. METHODS: In this study, we evaluated the performance of a newly introduced chemiluminescent immunoassay assay (CLIA) for the determination of serum HSV‐1 and HSV‐2 immunoglobulin G (IgG) antibodies. RESULTS: The functional sensitivity of detecting HSV‐1 and HSV‐2 IgG were 0.7 Index and 0.6 Index, respectively. The repeatability and the total imprecision coefficient of variations were both below 10%, and the recoveries of these assays ranged from 90% to 110%. High concentration of hemoglobin, lipids, and bilirubin in samples did not affect the results. The infective rates of HSV‐1 and HSV‐2 were 919 (87.5%) and 169 (16.1%), respectively. HSV‐1 seroprevalence was significantly higher than that of HSV‐2 (P < 0.001). CONCLUSION: CLIA is an excellent method for HSV‐1 and HSV‐2 IgG measurement and can be used as a routine screening test. The infective rate of HSV was pretty high among women before pregnancy or in the period of pregnancy in Beijing.

Human immunodeficiency virus (HIV) screening assays have improved from single-antigen detection to detection of antigen-antibody combinations. However, concerns have been raised over the potential for false-positive results in antigen-antibody combination assays. The present study investigated the clinical effectiveness of HIV antigen/antibody (HIV Ag/Ab) combination screening by chemiluminescence microparticle immunoassay (CMIA) in over 88,000 samples from an HIV low-prevalence area of Beijing, China. The HIV Ag/Ab CMIA screening results were consistent with those obtained by Western blot and HIV-RNA testing, and had an accuracy of 99.74% (Kappa index=0.98). False-positive results were more common for women affected by clinical interfering factors (e.g., kidney disease, tumors) than for men (80.95% vs. 15.09%, P

In the past few years, because of providing a closed system that allowed for collection, transport, processing, sampling, and storage of specimens, serum separator tubes gained widespread acceptance gradually in China. However, some limitations associated with gel tubes had been observed, for example, gel and analyte stability. In order to circumvent these problems, a new tube (BD Vacutainer(®) SST™ II Plus (BD SST™ II Plus)) containing a new gel was released by BD with respect to analyte and gel stability. We investigated the performance of BD SST™ II Plus tubes for special proteins testing using BD Vacutainer(®) Serum Glass Tubes (BD Serum Glass) as controls.Equivalence between these two types of tubes was demonstrated for all analytes at initial time, and data for all analytes except complement 3 (C3) and complement 4 (C4) indicated comparable stability over time in these two types of tubes. Concentration of C3 and C4 tended to increase with preservation time up to 72 hr in BD Serum Glass tubes. The stability of C3 and C4 was better in BD SST™ II Plus, which was demonstrated at timepoints up to 48 hr. We conclude that BD SST™ II Plus was suitable for collection and storage of samples for special proteins testing. J. Clin. Lab. Anal. 25:203–206, 2011. © 2011 Wiley‐Liss, Inc.

To primarily investigate the changing mode of anti-SARS coronavirus IgG antibody in clinically diagnosed SARS patients and the possibility of subclinical infection in physicians and nurses through close association with SARS patients.The plasma levels of anti-SARS coronavirus IgG antibody of 57 normal subjects, 127 physicians and nurses worked in SARS wards for one month and 73 SARS patients with different course of SARS were measured by enzyme linked immunosorbent assay.Plasma anti-SARS coronavirus IgG antibody was not detected in normal subjects and the clinical personnel. After 0-7 days, 8-10 days, 11-14 days, 15-20 days of onset of disease, the positive rates were 0.33%, 52%, 86% respectively, and the general positive rate was 61%.The specificity and sensitivity of ELISA to detect plasma anti-SARS IgG antibody were satisfactory. Cases with positive reaction could be diagnosed as patients already infected by the virus. The specific IgG antibody didn't emerge in some patients in the early stage of the disease, and the negative results didn't indicate that they were not infected. And follow-up investigation should be made in those patients. Unlike common epidemic infectious diseases, SARS probably hadn't the potentiality of subclinical infection.

To avoid the staff's infection and environmental contamination, we establish the rules suited for severe infectious disease in our laboratory.(1) Enhance the staff's notion of safety, institute a rule for biological safety and make sure the responsibility of safety for everybody. (2) Set up a special laboratory or area for detection of specimens associated with SARS, appoint the staff specially assigned for the task. The approach to environmental cleaning and disinfection in the laboratory is according to the guidance. (3) Laboratory staff should take precaution when entering and leaving laboratory according to the guidance. (4) Collection, transportation, pre-disposal and storage of specimen from patients with SARS for testing should be done in leak-resistant environment. These specimen should be performed in biological safety cabinet. All Clinical waste must be placed in an appropriate leak-resistant biohazard bag or container, labeled and disposed of safely.Since the outbreak of SARS, no staff was infected with SARS in our clinical laboratory.Our precaution is feasible and effective. A series of rules ensure the safety for the laboratory staffs and environment.