Objective To validate the performance of six enzymatic glycated albumin reagents and evaluate their clinical application.Methods The performance of six enzymatic glycated albumin reagents(labled as A,B,C,D,E,F) from Beijing Jiuqiang Co, Beijing Lideman Co,Ningbomeikang Co, Beijing Haomai Co, Sichuan Maike Co and Asahi Kasei Co were assessed on Olympus AU5800 automatic biochemistry analyzer.According to the standard of CLSI,the precision,interference and linear correlation of these reagents were assessed.To assess the accuracy of GA% ,we used GA standard material whose value had been assigned using ID-LC/MS method provided by ReCCS.To do the method comparison and determine the consistency of assay, 50 fresh serum samples of T2DM outpatient and 80 fresh serum samples of apparently healthy people in Jan 2016 were tested using six kits.According to the EP28-A3C protocol, the reference range for GA%was validated in 122 apparently healthy individuals undertaking medical examination from January to February 2016 in PUMC.Results The precision,and the ability of anti-interference of the six reagents were good.The accuracy percentage deviation of six reagents was-19.3%-9.2%.The correlation coefficient of domestic reagents A to E and imported reagents F in the determination of GA% was 0.966-0.999, the average absolute bias was 7.0%-10.4%.The coincidence rate of A-E and F in determining abnormal GA% was between 88.5% and 96.9%.The coincidence rate was increased after switching to the reference range for preliminary clinical evaluation.Conclusion Six GA enzymatic kits used in automatic biochemical analyzer have high precision and strong anti-interference ability.Accuracy still needs to be improved.

OBJECTIVE To explore mecha-nisms of imperatorin on regulating P-glycoprotein(P-gp)in blood-brain barrier(BBB)based on net-work pharmacology combined with in vitro experi-ment.METHODS Drug targets were predicted using the Pharmapper and Swiss targets data-bases;disease targets were obtained through the Genecards database;intersections between drugs and disease targets were screened by Cytoscape software;the obtained core targets were used to construct protein-protein interaction(PPI)network,gene ontology(GO)functions,and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The effects of imperatorin(20,50,100 μ mol·L-1)on P-gp activity were monitored in hCMEC/D3in vitro BBB model,and the effects of imperatorin on the expression of target proteins were verified using Western blot method.RESULTS 55 drug targets and 3102 disease targets were obtained from the network pharmacology screening,and 37 core targets were obtained after the combination.Enrichment analysis showed that core targets were closely related to chemical synaptic trans-mission regulation,neurotransmitter receptor activity,proteinkinaseregulationactivity,G protein-coupled receptor signaling pathway,neural active ligand receptor interaction pathway,PI3K-Akt sig-naling pathway,VEGF signaling pathway,etc..In vitro experimental validation suggested that all tested concentration groups of imperatorin signifi-cantly reduced the activity and expression of P-gp,which were achieved by significantly downregu-lating the phosphorylation levels of PI3K and Akt,and repressing the expression of VEGFR2 pro-tein.CONCLUSION Network pharmacology was used to predict the core targets and signaling pathways of imperatorin on regulating P-gp in BBB and relevant validation was conducted through in vitro experiments,providing a refer-ence basis for further exploration of the mecha-nisms of imperatorin on regulating P-gp in BBB.

Objective To establish a method for quantification of aldosterone (ALD) in urine by LC-MS/MS.Methods This study was the establishment and validation of methodology for urine ALD using LC-MS/MS.The urine samples were hydrolyzed at 37 ℃ by hydrochloric acid and the deuterated isotope internal was then added , followed by protein precipitation and anion exchange solid phase extraction (SPE). After SPE, the eluates were detected in the negative electro-spray ionization mode and multiple reaction monitor mode.The linearity, lower limits of quantification , precision and recovery of LC-MS/MS were evaluated.Urine and serum ALD of 80 subjects were measured by LC-MS/MS to evaluate the correlation of ALD detected in serum and 24 h urine.70 urine samples were collected and measured with LC-MS/MS and CLIA method for ALD comparison.14 participants were recruited to study the distribution of urine ALD in apparent healthy population .Results The analytical time was 4.5 min.Linearity of ALD was good in the range of 2-1 000 pg/ml (R2＞0.990); the repeatability and CV of ALD were less than 4.0% and 5.0%respectively; the recovery of urine ALD ranged between 100.4%and 108.2%; the lower limits of detection was 1 pg/ml.The correlation between urine and serum ALD was 0.396.The method comparison resulted in linear equation Y＝0.998 8X+0.046 4(r＝0.991).The distribution of urine ALD in apparent healthy subjects were 0.74-17.09 μg/24 h.Conclusion A reliable and specific LC-MS/MS method for urine ALD was established.And condition of the acid hydrolyzation for urine ALD was optimized .The method is simple, rapid and it can be used for the diagnosis of primary aldosteronism.

Objective To investigate the changes of prevalence of hyperuricemia ( HUA) and its correlations with blood glucose and lipid in healthy adults receiving physical examination at Peking Union Medical College Hospital (PUMCH) from 2012 to 2017. Meth-ods An observational approach was adopted for the data analysis.The test results of uric acid (UA),fasting blood glucose (FBG),to-tal cholesterol (TC),triacylglycerol (TG),low density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C), creatinine (Cr) and Urea of 399 089 cases (206 881 males and 192 208 females) at PUMCH from January 2012 to December 2017 were collected and statistically analyzed.Results The total prevalence of HUA was 17.4% in which the prevalence of males was signif-icantly higher than that of females (25.6% vs 8.5%,χ2＝20 234.850,P＜0.01).During the years of 2012 to 2017,the prevalence of HUA was 26.5%,24.7%,28.6%,23.9%,24.8% and 24.5% in males,and 13.8%,6.3%,7.9%,6.1%,6.2% and 6.8% in females for each year respectively.The prevalence of HUA in males aged 18 to 64 years old was significantly higher than that in the age-matched fe-males (all P＜0.05).However, the prevalence of HUA in males aged≥65 years old was similar to the age-matched females.There was no statistically significant difference of HUA prevalence between males and females aged ≥65 in 2013,2015,2016 and 2017 ( χ2＝1.792,0.017,1.440 and 0.205 respectively;all P＞0.05).The percentages of hyperlipidemia in both males and females of HUA group were higher than those of non-HUA group respectively (all P＜0.01).The percentage of hyperglycemia in males of non-HUA group was higher than that of HUA group,but the percentage of hyperglycemia in females of non-HUA group was lower than that of HUA group ( all P＜0.01).High levels of TC,TG and FBG were risk factors of HUA with increased OR values in increased concentrations of TC,TG and FBG,respectively.Conclusion During the recent 6 years, in healthy adults receiving physiced examination at PVMCH, the preva-lence of male HUA diagnosed was at overall high level,but the prevalence of female HUA was in decreasing and relatively stable trend. Hyperlipidemia and hyperglycemia should be the risk factors of HUA.

Objective:To compare the differences of reference intervals (RI) established by two types of indirect methods for 34 biochemical analytes, and to explore the possible factors that affect the consistency of the two methods.Methods:This was a retrospective study. Based on data of albumin (Alb), alkaline phosphatase (ALP), alanine aminotransferase (ALT), apolipoprotein A1(ApoA1), ApolipoproteinB (ApoB), aspartate aminotransferase (AST), calcium (Ca), cholinesterase (ChE), chloride (Cl), creatinine (Cr), high-sensitivity C-reactive protein (hsCRP), Cystatin (CysC), direct bilirubin (DBil), free fatty acid (FFA), glycated albumin(GA), gamma-glutamyltransferase (GGT), glucose (Glu), high density lipoprotein cholesterol (HDL-C), potassium (K), lactate dehydrogenase (LD), low density lipoprotein cholesterol (LDL-C), lipoprotein a [Lp (a)], sodium (Na), phosphorus (P), prealbumin (PA), superoxide dismutase (SOD), total bile acid (TBA), total bilirubin (TBil), total cholesterol (TC), total carbon dioxide (TCO 2), triglyceride (TG), total protein (TP), uric acid (UA) and urea (UR) of individuals who underwent physical examination at Peking Union Medical College Hospital from January 1, 2018 to December 31, 2019, Box-Cox algorithm was used to improve the data distribution and Tukey method was used to identify outliers. Variance component model was established, and standard deviation ratio (SDR) was calculated to determine whether the RIs of 34 biochemical analytes should be established according to age or sex The non-parametric method and kosmic algorithm were used to establish the RIs and 90% confidence intervals (CIs) of 34 biochemical analytes, and the coincidence of the 90% CIs of the reference limits for two methods was compared. Results:The skewness coefficients of ALP(male, female18-59), ALT, AST, hsCRP, DBil, GGT, Lp (a), TBA, TBil, TG, Glu, HDL-C(male) and CysC, GA, UR in the elderly group deviated from 0, and their kurtosis coefficients also deviated from 3. For these biochemical analytes, the point estimates of the RIs established by the two methods differed greatly and the 90% CIs did not overlap. The analytes with good normality were Alb, ApoA1, ApoB, Ca, ChE, Cl, Cr(E), CysC(18-59), FFA, GA(18-59), HDL-C(female), K, LDL-C, Na, P, PA, SOD, TC, TCO 2, TP and UR. The consistency is good. Except for Ca, 90% CIs of reference limits for some analyte between the two methods coincide with each other. Conclusions:The consistency of different indirect methods is affected by the normality of data.

Objective To investigate the prevalence and possible factors of hypouricemia in Peking Union Medical College Hospital.Methods A retrospective investigation.Serum uric acid, lipids, glucose and other chemistry tests were analyzed among 83176 outpatients(Male:30795,Female:52381), 15849 inpatients(Male:7402,Female:8447)and 24081 healthy subjects(Male:11859,Female:12222)in Peking Union Medical College Hospital from December 2015 to April 2016.Grouped by gender and age, the prevalence of hypouricemiawas analyzed in all subjects and the etiology and possible risk factors of hypouricemia were explored among all patients.Results The serum uric acid of outpatients,inpatients and healthy subjects were 286(235-348)μmol/L, 282(226-348)μmol/L and 298(244-358)μmol/L, respectively.And the prevalence were 0.6%(499/83176),2.5%(390/15849)and 0.2%(39/24081), respectively.The prevalence of hypouricemia ofwomen was significantly higher than that ofmen(outpatients:0.7%vs 0.4%,P<0.001;inpatients:2.8%vs 2.1%,P=0.004;healthy subjects:0.30%vs 0.04%, P<0.001).After analyzing 507 hypouricemia patients, the top three clinical diagnoses that related with hypouricemia were kidney diseases, tumor and rheumatic diseases.Compared with the control group, the prevalence of hypouricemia in hypertriglyceridemia group and group with eGFR higher than 90 ml/(min· 1.73 m2)were lower(OR:0.33, 95% CI:0.21-0.50; OR:0.16, 95% CI:0.09-0.29), and the prevalence of hypouricemia in hyperglycemia group was higher(OR:1.62, 95% CI:1.12-2.35). Conclusion The prevalence of hypouricemia of Chinese women was higher than that of men and may be related with TG,Glu and eGFR.

Objective:The characteristics of women with false elevated testosterone were analyze and the literature was reviewed to provide reference for clinical laboratory identification of false elevated testosterone.Methods:The characteristics of three patients with false elevated testosterone in Peking Union Medical College Hospital were analyzed retrospectively, and the results of different detection platforms and methods for the determination of testosterone levels were compared. International and domestic literatures related to false elevation of testosterone and detection methods of testosterone were searched for a comprehensive analysis from PUBMED and CNKI.Results:The levels of testosterone in 3 female patients were elevated by immunoassay and normal by mass spectrometry. They were excluded from the diagnosis of hyperandrogenemia. A total of 38 literatures related to testosterone detection were retrieved, of which 9 case reports of pseudohyperandrogenemia, among which 12 cases of pseudohyperandrogenemia were reported in 2 domestic literatures in 2021. All cases were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Previous studies have clearly indicated that the result of routine immunoassay in clinical laboratory for the determination of female testosterone have poor correlation with the results of LC-MS/MS, with varying degrees of deviation.Conclusions:Immunoassay tests for female testosterone is susceptible to interference and lead to elevated false results. It is suggested that clinical laboratories evaluate the detection methods used and establish a identification program, and confirm samples with suspected pseudoelevated testosterone elevation using other immune platforms or LC-MS/MS.

Background: Thyroid diseases are highly prevalent worldwide, but their diagnosis remains a challenge. We established reference intervals (RIs) for thyroid-associated hormones and evaluated the prevalence of thyroid diseases in China. Methods: After excluding outliers based on the results of ultrasound screening, thyroid antibody tests, and the Tukey method, the medical records of 20,303 euthyroid adults, who visited the Department of Health Care at Peking Union Medical College Hospital from January 2014 to December 2018, were analyzed. Thyroid-associated hormones were measured by the Siemens Advia Centaur XP analyzer. The RIs for thyroid-associated hormones were calculated according to the CLSI C28-A3 guidelines, and were compared with the RIs provided by Siemens. The prevalence of thyroid diseases over the five years was evaluated and compared using the chi-square test. Results: The RIs for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were 0.71–4.92 mIU/L, 12.2–20.1 pmol/L, 3.9–6.0 pmol/L, 65.6–135.1 nmol/L, and 1.2–2.2 nmol/L, respectively. The RIs of all hormones except TT4 differed significantly between males and females. The RIs of TSH increased with increasing age. The prevalence of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was 0.5% and 0.8%, 0.2% and 0.6%, 3.8% and 6.1%, and 3.3% and 4.7% in males and females, respectively, which differed from those provided by Siemens. Conclusions Sex-specific RIs were established for thyroid-associated hormones, and the prevalence of thyroid diseases was determined in the Chinese population.

BACKGROUND: Epilepsy accounts for a significant portion of the global disease burden. However, little is known about the disease burden of epilepsy in China and its provinces. METHODS: We assessed the burden of epilepsy in China and its provinces, municipalities, and autonomous regions from 1990 to 2019. Burden was measured as incidence, prevalence, deaths, years lived with disability, years of life lost, and disability-adjusted life years (DALYs), by age, sex, year, and province. We used the Socio-Demographic Index (SDI) to determine the association between the provincial development level and age-standardized DALY rates of epilepsy from 1990 to 2019. RESULTS: In 2019, epilepsy caused 1367.51 thousand (95% uncertainty interval [UI]: 979.92-1837.61 thousand) DALYs, and the age-standardized DALY rate was 99.77 (95% UI: 71.33-133.52)/100,000. The age-standardized incidence and prevalence rates for epilepsy in China were 24.65/100,000 and 219.69/100,000, increased by 45.00% (95% UI: 8.03-98.74%) and 35.72% (95% UI: 0.47-86.19%) compared with that in 1990, respectively. From 1990 to 2019, the proportion of DALY caused by epilepsy in the age group under 25 years steadily decreased. The proportion of DALYs caused by epilepsy in people aged 50 years and over increased from 9.45% and 10.22% in 1990 to 29.01% and 32.72% for male and female individuals in 2019, respectively. The highest age-standardized mortality rates were seen in Tibet (4.26 [95% UI: 1.43-5.66]/100,000), Qinghai (1.80 [95% UI: 1.15-2.36]/100,000), and Yunnan (1.30 [95% UI: 0.88-1.62]/100,000), and the lowest mortality rates were in Guangdong (0.48 [95% UI: 0.39-0.64]/100,000), Zhejiang (0.56 [95% UI: 0.44-0.70]/100,000), and Shanghai (0.57 [95% UI: 0.41-0.73]/100,000). The age-standardized DALY rates across the country and in provinces, municipalities, and autonomous regions generally decreased as their SDI increased. CONCLUSIONS The disease burden of epilepsy is still heavy in China, especially in the western provinces. The incidence and prevalence of epilepsy increased between 1990 and 2019, and the burden of epilepsy in the elderly increases gradually. This study provides evidence on epilepsy prevention and care of different regions in China.
Aged ; Humans ; Male ; Female ; Middle Aged ; Adult ; Global Burden of Disease ; China/epidemiology* ; Quality-Adjusted Life Years ; Cost of Illness ; Epilepsy/epidemiology* ; Prevalence

Objective: To compare the consistency of thyroid stimulating hormone (TSH) results from four chemiluminescence assays. Methods: A total of 102 fresh serum samples from Peking Union Medical College Hospital during March 2018 and April 2018 were collected for precision evaluation and methodological comparison referring to CLSI EP15-A2 and EP9-A2 protocols. The levels of serum TSH were detected by Abbott i2000 (system A), Beckman DXI800 (system B), Siemens ADVIA Centaur XP (system C) and Roche e601 (system D) automatic chemiluminescence analyzers and their matching reagents, respectively. The obtained results were compared with the passing-bablok and Bland Altman methods. Taking 0.27 μIU/mL and 5.33 μIU/mL as the medical decision level, the expected bias of each detection system was compared. Results: The precisions of systems A,B,C and D were 1.7%-3.3%， 2.3%- 3.9%，0.7%-2.3% and 0.6%-1.5%,respectively. The median (P 25,P 75) of TSH concentrations detected by systems A,B,C and D were 1.898 (0.518,4.809)μIU/mL, 2.819 (0.719,7.020)μIU/mL,2.502 (0.692,6.888)μIU/mL and 3.105 (0.886, 7.905)μIU/mL, respectively. The coefficients of determination (R 2 ) of regression equation were above 0.975 for 4 detection systems. The correlation coefficients (r), intercepts and slopes of 4 detection systems were 0.993 5-0.997 1, 0-0.06 and 0.59-1.15, respectively, and systems B and C had the best correlations with 1.02 of slope and 0 of intercept. The deviation plot showed that the bias% of 4 detection systems was between -48.1% and 17.3%. Among them, systems A and D had the largest bias, while systems B and C had the lowest bias. The expected bias of 4 detection systems at the medical decision level was -40.7%-37.2%. Conclusion The consistency between Beckman and Siemens TSH detection systems is good, while those of Roche and Abbott TSH detection systems are different from the other two.