Plasma Steroid Profiling Combined With Machine Learning for the Differential Diagnosis in Mild Autonomous Cortisol Secretion From Nonfunctioning Adenoma in Patients With Adrenal Incidentalomas.

OBJECTIVE: To assess the diagnostic value of combining plasma steroid profiling with machine learning (ML) in differentiating between mild autonomous cortisol secretion (MACS) and nonfunctioning adenoma (NFA) in patients with adrenal incidentalomas. METHODS: The plasma steroid profiles data in the laboratory information system were screened from January 2021 to December 2023. EXtreme Gradient Boosting was applied to establish diagnostic models using plasma 24-steroid panels and/or clinical characteristics of the subjects. The SHapley Additive exPlanation (SHAP) method was used for explaining the model. RESULTS: Seventy-six patients with MACS and 86 patients with NFA were included in the development and internal validation cohort while the external validation cohort consisted of 27 MACS and 21 NFA cases. Among 5 ML models evaluated, eXtreme Gradient Boosting demonstrated superior performance with an area under the curve of 0.77 using 24 steroid hormones. The SHAP method identified 5 steroids that exhibited optimal performance in distinguishing MACS from NFA, namely dehydroepiandrosterone, 11-deoxycortisol, 11ß-hydroxytestosterone, testosterone, and dehydroepiandrosteronesulfate. Upon incorporating clinical features into the model, the area under the curve increased to 0.88, with a sensitivity of 0.77 and specificity of 0.82. Furthermore, the results obtained through SHAP revealed that lower levels of testosterone, dehydroepiandrosterone, low-density lipoprotein cholesterol, body mass index, and adrenocorticotropic hormone along with higher level of 11-deoxycortisol significantly contributed to the identification of MACS in the model. CONCLUSIONS: We have elucidated the utilization of ML-based steroid profiling to discriminate between MACS and NFA in patients with adrenal incidentalomas. This approach holds promise for distinguishing these 2 entities through a single blood collection.

Radial Magnetic Levitation and Its Application to Density Measurement, Separation, and Detection of Microplastics.

This work describes the development of radial magnetic levitation (MagLev) using two radially magnetized ring magnets to solve the problem of limited operational spaces in standard MagLev and the major shortcoming of a short working distance in axial MagLev. Interestingly and importantly, we demonstrate that for the same magnet size, this new configuration of MagLev doubles the working distance over the axial MagLev without significantly sacrificing the density measurement range, whether for linear or nonlinear analysis. Meanwhile, we develop a magnetic assembly method to fabricate the magnets for the radial MagLev, where multiple magnetic tiles with single-direction magnetization are used as assembly elements. On this basis, we experimentally demonstrate that the radial MagLev has good applicability in density-based measurement, separation, and detection and show its advantages in improving separation performance compared with the axial MagLev. The open structure of two-ring magnets and good levitation characteristics make the radial MagLev have great application potential, and the performance improvement brought by adjusting the magnetization direction of magnets provides a new perspective for the magnet design in the field of MagLev.

Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data.

Thyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052-3.393 µIU/ml, 1.01-1.54 ng/dl, and 2.51-3.66 pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.

Data mining: traditional spring festival associated with hypercholesterolemia.

BACKGROUND: Serum lipid concentrations are affected by long-term high-fat diets; thus, we hypothesize that lipid levels increase after the Spring Festival in China. METHOD: In total, 20,192 individuals (male: n=10,108, female: n=10,084) were enrolled in this retrospective cross-sectional study based on clinical data from the Laboratory Information System (LIS) and Hospital Information System (HIS) in Peking Union Medical College Hospital from 2014 to 2018. Total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were analyzed. RESULTS: The serum TC [male vs. female: (4.71 ± 0.90 vs. 4.56 ± 0.85) mmol/L], TG [male vs. female: (1.71 ± 1.56 vs. 1.02 ± 0.68) mmol/L], and LDL-C [male vs. female: (3.01 ± 0.77 vs. 2.73 ± 0.74) mmol/L] levels were significantly higher in males than in females (P < 0.001); serum HDL-C [male vs. female: (1.18 ± 0.28 vs. 1.50 ± 0.34) mmol/L] was significantly lower in males (P < 0.001). In February, the TC, TG, and LDL-C levels were 8.4%, 16.3%, and 9.3% higher than the lowest levels recorded, respectively. The prevalence of dyslipidemia of the two weeks before the Spring festival was significantly lower than that of the first week after the Spring festival (43.6% (168/385) vs. 54.1% (126/233), P=0.007). Additionally, the prevalence of dyslipidemia was statistically higher in the first week after the Spring Festival than in May-January. CONCLUSION: Higher TC, TG, and LDL-C in winter could be associated with high-fat diets during the Spring Festival. The Spring Festival was immediately followed by a higher lipid concentrations. Thus, we don't recommend lipid assessment or physical examination immediately after the holiday especially Spring festival.

LC-MS/MS quantification of progesterone in ovariectomized miniature swine and its application for preliminary pharmacokinetic study of a novel vaginal sustained release system.

OBJECTIVE: We here established a simple, fast, robust and sensitive LC-MS/MS method and validated as well for the quantitative analysis of progesterone (PGT) in ovariectomized (OVX) miniature swine plasma. The method was successfully applied to characterize the pharmacokinetics of a progesterone vaginal drug delivery system. METHODS: Megestrol acetate was utilized as an internal standard (IS). The separation and detection of PGT from endogenous interference was performed successfully by liquid chromatography with gradient elution and mass spectrometry equipped with positive ESI source using MRM mode. The EVA intravaginal rings (IVRs) were manufactured by hot-melt extrusion (HME), afterward were administrated vaginally to OVX minipigs to evaluate PK study. RESULTS: The calibration curve for swine plasma samples across the concentration ranged between 0.25 ng/mL and 100 ng/mL. The intra- and inter-assay accuracy and precision were lower than ±5% and 5.88%, respectively. Recoveries of PGT and IS were ranging from 114-119% and 96.5-112%, respectively. In vitro study showed that the EVA IVRs release 18 mg/day of PGT continuously over 7 days, and corresponding mean PGT plasma concentration in OVX minipigs (CAVG) was 4.892 ng/mL. CONCLUSION: All the study produced reliable results for the measurement of PGT concentration in miniature swine plasma and the method was successfully applied to a PK study for PGT vaginal ring in miniature pigs, which may lay the foundation for further research on the progesterone preparations intended for in assisted reproductive technology.

Effects of calcium dobesilate (CaD) interference on serum creatinine measurements: a national External Quality Assessment (EQA)-based educational survey of drug-laboratory test interactions.

Objectives: Drug-laboratory test interactions (DLTIs) are one of the major sources of laboratory errors. Calcium dobesilate (CaD) interference on serum creatinine testing is a widespread problem that has long been ignored in China. A national EQA-based survey was launched to investigate the current status of CaD interference on creatinine routine methods used in China and enhance the education of CaD interference in clinical laboratories. Methods: A descriptive survey was developed to characterize the status quo of Chinese laboratory professionals' cognition to CaD interference. Four of survey samples which were spiked with/without interference additive were shipped to 175 participant laboratories. The target reference values from a reference measurement procedure were compared against the results from participating laboratories to evaluate the CaD interference on serum creatinine measurements using enzymatic method or Jaffé method. Results: The lack of knowledge of DLTIs and the barriers to collect information from pharmacological and laboratory data systems had become the main problems on implementing DLTIs education in China. A significant negative influence of CaD on enzymatic method was observed regardless of measurement platforms. Jaffé method was generally free from interaction with CaD but showed poor precision and accuracy at low creatinine concentrations. Conclusions: More efforts should be made to enhance the education of DLTIs in clinical laboratories in China.

Establishment of variation source and age-related reference interval models for 22 common biochemical analytes in older people using real-world big data mining.

BACKGROUND: the ageing population has increased in many countries, including China. However, reference intervals (RIs) for older people are rarely established because of difficulties in selecting reference individuals. Here, we aimed to analyse the factors affecting biochemical analytes and establish RI and age-related RI models for biochemical analytes through mining real-world big data. METHODS: data for 97,220 individuals downloaded from electronic health records were included. Three derived databases were established. The first database included 97,220 individuals and was used to build age-related RI models after identifying outliers by the Tukey method. The second database consisted of older people and was used to establish variation source models and RIs for biochemical analytes. Differences between older and younger people were compared using the third database. RESULTS: sex was the main source of variation of biochemical analytes for older people in the variation source models. The distributions of creatinine and uric acid were significantly different in the RIs of biochemical analytes for older people established according to sex. Age-related RI models for biochemical analytes that were most affected by age were built and visualized, revealing various patterns of changes from the younger to older people. CONCLUSION: the study analysed the factors affecting biochemical analytes in older people. Moreover, RI and age-related RI models of biochemical analytes for older people were established to provide important insight into biological processes and to assist clinical use of various biochemical analytes to monitor the status of various diseases for older people.

Comparison of four matrixes for diluting insulin in routine clinical measurements.

OBJECTIVE: In our laboratory, 2.36% (6626/280765) samples obtained for insulin evaluation have serum insulin concentrations higher than 300 mU/L, resulting in curves outside the linear range in the insulin release test (IRT). Accordingly, using appropriate dilution protocols to determine insulin concentration accurately is important. Here, we compared the effectiveness and economy of four different solutions for diluting high-insulin serum in routine clinical measurements. METHOD: Residual serum samples with high-insulin concentrations ranging from 200 to 300 mU/L were collected in Peking Union Medical College Hospital from August to November 2017. Four different matrixes including a Siemens original diluent, pure water, 0.9% NaCl, and low-insulin serum (labeled as A to D, respectively) were used to dilute the serum in the ratios of 1:2, 1:5, and 1:10. RESULTS: We found that the linear correlation coefficients of A to D were higher than 0.9. The recovery rates of A to D were 86.4%-104.0%, 73.2%-99.3%, 76.4%-101.3%, and 84.2%-99.7%, respectively. We conclude that the use of 0.9% NaCl, pure water, or low-insulin serum to dilute high-serum insulin (>300 mU/L) is feasible and cost-effective. CONCLUSION: We recommend a dilution factor of 1:5 on a Siemens ADVIA Centaur XP® instrument. The clinically reported range was 0.5-1500 mU/L. For specific samples (>1500 mU/L), we recommended using low-insulin serum samples for dilution.

Measuring lipoprotein-associated phospholipase A2 activity in China: Protocol comparison and recalibration.

BACKGROUND: Lp-PLA2 is a novel inflammation marker in cardiovascular disease. While several manufactures have registered Lp-PLA2 activity reagents, few studies have investigated the consistency among these assays. In this study, we compared and recalibrated Lp-PLA2 activity assays. METHODS: Serum samples from 110 patients and 140 healthy individuals were collected for method comparison and reference interval validation, respectively. Fresh human serum pools (847 and 442 U/L) were used for recalibration. Lp-PLA2 activity was analyzed using all five assays with a Beckman AU 5800 analyzer. Passing-Bablok regression equations and Bland-Altman plots were used to estimate the relationship and bias among the results. A 2.5% confidence interval (CI) and 97.5% CI were used to establish a laboratory reference interval. RESULTS: Assay imprecision varied from 0.8%-2.9%, while the overall coincidence rates ranged from 75.5%-98.2%. Passing-Bablok regression shows excellent linear correlation between Evermed and Diasys (R2  = 0.999), while that between Diazyme and Evermed was poor (R2  = 0.846). The R2 and correlation coefficient r among assays were 0.846-0.999 and 0.8947-0.9993, respectively. The mean bias percentages ranged from -71.5%-1.6% and -2.0%-11.6% before and after recalibration. As Diazyme and Diasys were not comparable, the Diazyme assay was not recalibrated. The reference intervals determined for Diasys, Evermed, Hengxiao, and Zybio were 184-605, 208-704, 81-328, and 273-696 U/L, respectively. CONCLUSIONS: Our results indicate that recalibration increased assay agreement and also highlight the need for each laboratory to establish its own reference interval for Lp-PLA2 activity.

Preparation and in vitro/in vivo evaluation of anastrozole reservoir-type intravaginal ring.

This report details the preparation of anastrozole (ATZ) reservoir-type intravaginal ring (IVR) and the detection of the concentration of ATZ in beagle dog plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS). An ATZ reservoir-type IVR which included ATZ silicone elastomer core and a nonactive silicone layer was manufactured by reaction injection moulding at 80°C for 20 min. An in vitro release experiment was performed under sink conditions and the samples were determined by high-performance liquid chromatography. A bioanalytical method was developed and validated for determination of ATZ in beagle dog plasma for IVR development. The analytical method consisted of the extraction of plasma samples and determination of ATZ by LC-MS/MS using buspirone as the internal standard. Separation was achieved on a Kinetex-C18 110A column (3 × 30 mm, 2.6 µm, Phenomenex) using step-gradient mobile phase and an isocratic flow rate consisting of formic acid. Protonated ions formed by a turboion spray in the positive mode was used to detect the analyte (ATZ) and internal standard. The MS-MS detection was performed on a triple quadrupole mass spectrometer equipped with electrospray ionization source. The mass spectrometer was operated in the multiple reaction monitoring mode. The mass transition ion-pair was followed as m/z from 294.10 to 225.08 for anastrozole and m/z from 386.23 to 122.11 for buspirone. The results proved that the correlation between in vitro and in vivo analyses was relatively good.

Is it necessary for all samples to quantify 25OHD2 and 25OHD3 using LC-MS/MS in clinical practice?

BACKGROUND: The demand for vitamin D testing is increasing in China. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) immunoassay is specific and accurate but requires expensive equipment, experienced operators, and complicated pretreatment of serum. Automated immunoassays are simple and convenient but only determine total 25-hydroxyvitamin D (25OHD). The objective of this study was to quantify 25OHD2 and 25OHD3 in patients to assist clinical physicians and laboratory directors in choosing the most appropriate method to determine 25OHD. METHODS: Vitamin D testing was conducted for 23,695 patients in Peking Union Medical College Hospital from May 2015 to January 2017. Using this large data set, the prevalence and levels of 25OHD2 were analyzed. LC-MS/MS was used to separately determine 25OHD2 and 25OHD3. RESULTS: 25OHD2 (≥2.5 ng/mL) was detected in 16.4% (3877/23,695) of patients. Males had a significantly lower incidence of detectable 25OHD2 (p<0.01); 1077 (13.9%) samples contained detectable 25OHD2 (median: 3.7 ng/mL; 2.5%-97.5%: 2.5-17.2 ng/mL). For females, 2800 (17.5%) samples contained detectable 25OHD2 (median: 4.0 ng/mL; range: 2.5-20.6 ng/mL). Of the 3877 patients with detectable 25OHD2, males had a significantly higher level of 25OHD3 (p<0.01). There was no significant difference in total 25OHD. The proportion of 25OHD2 in total 25OHD was 1.3%-100%; 87.5% (3391/3877) of the samples contained <10 ng/mL 25OHD2. 25OHD2 negatively correlated with 25OHD3 (r=-0.197, p<0.01) and positively correlated with total 25OHD (r=0.217, p<0.01). CONCLUSIONS: Prevalence of 25OHD2 in patients tested for vitamin D is relatively high in China. 25OHD2 is significantly negatively correlated with 25OHD3.

Establishing reference intervals for sex hormones and SHBG in apparently healthy Chinese adult men based on a multicenter study.

BACKGROUND: Measuring sex hormones is essential in diagnosing health issues such as testicular dysfunction, male infertility and feminization syndrome. However, there are no reports on reference intervals (RIs) in Chinese men. We conducted a nationwide multicenter study to establish RIs for seven sex hormones (luteinizing hormone [LH], follicle-stimulating hormone [FSH], prolactin [PRL], total testosterone [TT], free testosterone [FT], bioavailable testosterone [BAT] and estrogen [E2]), as well as sex hormone-binding globulin (SHBG). METHODS: In 2013, 1043 apparently healthy adult men from five representative cities in China (Beijing, Hangzhou, Guangzhou, Dalian and Urumqi) were recruited; hormones were measured using an automated immunoassay analyzer. Multiple regression analysis (MRA) was performed to identify sources of variation (SVs) that might influence the hormone serum levels. RIs were computed using the parametric method. RESULTS: Dalian and Hangzhou had significantly higher E2 values than other cities; age was a major source of variation for FSH, LH, PRL, SHBG, FT and BAT. FSH, LH and SHBG increased significantly with age, while PRL, FT and BAT decreased with age. TT showed no significant age-related changes. Median (RIs) derived without partition by age were as follows: FSH, 5.6 (1.9-16.3) IU/L; LH, 4.2 (1.6-10.0) IU/L; PRL, 189 (88-450) mIU/L; E2, 85 (4.7-195) pmol/L; SHBG, 29.4 (11.5-66.3) nmol/L; TT, 15.6 (7.4-24.5) nmol/L; FT, 0.31 (0.16-0.52) nmol/L; and BAT, 8.0 (3.7-13.2) nmol/L. RIs were also derived in accordance with between-city and between-age differences. CONCLUSIONS: RIs were established for sex hormones and SHBG in apparently healthy Chinese men in consideration of age.

Asymmetric magnetic levitation for density-based measurement and analysis.

BACKGROUND: Magnetic levitation (MagLev) based on negative magnetophoresis represents a promising technology for density-based analysis and manipulation of nonmagnetic objects. This approach has garnered considerable interest across multiple fields, such as chemistry, materials science, and biochemistry, primarily due to its inherent simplicity, precision, and cost-effectiveness. However, it is essential to recognize that frequently used MagLev configurations, including standard MagLev and axial MagLev, are not without their limitations. These configurations often struggle to strike a balance between levitation performance, ease of operation, and visibility. Therefore, it is necessary to develop a new MagLev configuration to address the aforementioned issue. RESULTS: This work describes the development of an innovative MagLev, termed "asymmetric MagLev", achieved by combining a ring magnet and a cylinder magnet as up-down asymmetric magnetic field sources. The asymmetric design overcomes the physical obstacles along the centerline of the standard MagLev, offering unique open-structure advantages, including easy handling of samples, the ability to observe samples from the top or bottom, and no restrictions on the container height. Meanwhile, comparative analysis reveals a considerable enhancement in the working distance of the asymmetric MagLev without significantly sacrificing the measurement range compared to the axial MagLev. Notably, the asymmetric MagLev achieves a remarkable sensitivity of up to about 1.8 × 104 mm (g cm-3)-1, surpassing the axial MagLev by approximately 30 times. Furthermore, experimental results validate the successful application of the asymmetric MagLev in density measurement and quality detection of small-sized objects. SIGNIFICANCE: This pioneering configuration represents the first utilization of up-down asymmetric magnets in the field of MagLev. Through the integration of an axially magnetized ring magnet and a cylinder magnet, the asymmetric MagLev design overcomes the limitations associated with conventional MagLev configurations. This innovative design exhibits outstanding operational capabilities and levitation performance, making it suitable for a wide range of applications in density-based measurement and analysis.

Metabolomic biomarkers for benign conditions and malignant ovarian cancer: Advancing early diagnosis.

BACKGROUND: Ovarian cancer (OC) is a major global cause of death among gynecological cancers, with a high mortality rate. Early diagnosis, distinguishing between benign conditions and early malignant OC forms, is vital for successful treatment. This research investigates serum metabolites to find diagnostic biomarkers for early OC identification. METHODS: Metabolomic profiles derived from the serum of 60 patients with benign conditions and 60 patients with malignant OC were examined using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Comparative analysis revealed differential metabolites linked to OC, aiding biomarker identification for early-diagnosis of OC via machine learning features. The predictive ability of these biomarkers was evaluated against the traditional biomarker, cancer antigen 125 (CA125). RESULTS: 84 differential metabolites were identified, including 2-Thiothiazolidine-4-carboxylic acid (TTCA), Methionyl-Cysteine, and Citrulline that could serve as potential biomarkers to identify benign conditions and malignant OC. In the diagnosis of early-stage OC, the area under the curve (AUC) for Citrulline was 0.847 (95 % Confidence Interval (CI): 0.719-0.974), compared to 0.770 (95 % CI: 0.596-0.944) for TTCA, and 0.754 for Methionine-Cysteine (95 % CI: 0.589-0.919). These metabolites demonstrate a superior diagnostic capability relative to CA125, which has an AUC of 0.689 (95 % CI: 0.448-0.931). Among these biomarkers, Citrulline stands out as the most promising. Additionally, in the diagnosis of benign conditions and malignant OC, using logistic regression to combine potential biomarkers with CA125 has an AUC of 0.987 (95 % CI: 0.9708-1) has been proven to be more effective than relying solely on the traditional biomarker CA125 with an AUC of 0.933 (95 % CI: 0.870-0.996). Furthermore, among all the differential metabolites, lipid metabolites dominate, significantly impacting glycerophospholipid metabolism pathway. CONCLUSION: The discovered serum metabolite biomarkers demonstrate excellent diagnostic performance for distinguishing between benign conditions and malignant OC and for early diagnosis of malignant OC.

Magnetically driven capsules with multimodal response and multifunctionality for biomedical applications.

Untethered capsules hold clinical potential for the diagnosis and treatment of gastrointestinal diseases. Although considerable progress has been achieved recently in this field, the constraints imposed by the narrow spatial structure of the capsule and complex gastrointestinal tract environment cause many open-ended problems, such as poor active motion and limited medical functions. In this work, we describe the development of small-scale magnetically driven capsules with a distinct magnetic soft valve made of dual-layer ferromagnetic soft composite films. A core technological advancement achieved is the flexible opening and closing of the magnetic soft valve by using the competitive interactions between magnetic gradient force and magnetic torque, laying the foundation for the functional integration of both drug release and sampling. Meanwhile, we propose a magnetic actuation strategy based on multi-frequency response control and demonstrate that it can achieve effective decoupled regulation of the capsule's global motion and local responses. Finally, through a comprehensive approach encompassing ideal models, animal ex vivo models, and in vivo assessment, we demonstrate the versatility of the developed magnetic capsules and their multiple potential applications in the biomedical field, such as targeted drug delivery and sampling, selective dual-drug release, and light/thermal-assisted therapy.

Development and clinical evaluation of an online automated quality control system for improving laboratory quality management.

BACKGROUND: We developed an efficient online automated quality control (AUTO QC) system and tested its feasibility on automatic laboratory assembly lines. METHODS: AUTO QC is based on developed quality control software (Smart QC) and designed adaptable consumables before. We applied the system to two assembly lines in our laboratory. Using third-party quality control samples, we evaluated the impact of the online AUTO QC system on out-of-control rate, biosecurity risk, turnaround time (TAT) and cost. RESULTS: AUTO QC significantly decreased the occurrence rate of the Westgard quality control rules 13S/22S/R4s and 12S, representing out-of-control and warning, respectively. The out-of-control rates were reduced by 58%, and the potential biosecurity risk of the samples decreased by 90%. The AUTO QC implementation also reduced the median TAT (by 7 min), the number of full-time employees and the cost of the quality control samples (by 45%). CONCLUSIONS: The total laboratory AUTO QC system can improve the quality and stability of QC testing and reduce cost.

miR-29a and miR-142-3p downregulation and diagnostic implication in human acute myeloid leukemia.

Expression profiling of microRNAs (miRNAs) in most diseases might be popular and provide the possibility for diagnostic implication, but few studies have accurately quantified the expression level of dysregulated miRNAs in acute myeloid leukemia (AML). In this study, we analyzed the peripheral blood mononuclear cells (PBMCs) from 10 AML patients (subtypes M1 to M5) and six normal controls by miRNA microarray and identified several differentially expressed miRNAs. Among them miR-29a and miR-142-3p were selectively encountered in Northern blot analysis and their significantly decreased expression in AML was further confirmed. Quantitative real-time PCR in 52 primarily diagnosed AML patients and 100 normal controls not only verified the expression properties of these 2 miRNAs, but also established that the expression level of miR-142-3p and miR-29a in PBMCs could be used as novel diagnostic markers. A better diagnostic outcome was achieved by combining miR-29a and miR-142-3p with about 90% sensitivity, 100% specificity, and an area under the ROC curve (AUC) of 0.97. Our results provide insights into the involvement of miRNAs in leukemogenesis, and offer candidates for AML diagnosis and therapeutic strategy.

Water-based ferrofluid with tunable stability and its significance in nuclear wastewater treatment.

The treatment of nuclear wastewater is one of the most urgent and arduous tasks currently, but traditional adsorption materials are significantly limited in practice due to their high demands on auxiliary operations (e.g., shaking or centrifugation) caused by poor stability or recyclability. To tackle this challenge, a water-based ferrofluid composed of magnetic nanoparticles grown in polyethylenimine branches is reported and applied to nuclear wastewater treatment. It is demonstrated that the ferrofluid can keep stable spontaneously in a wide pH range (3-11) out of their ultra-small size, strong electropositivity as well as high charge buffering capacity to achieve shaker-free adsorption, and can be magnetically separated after the neutralization of their positive charge to achieve convenient recycle. Meanwhile, it is found that the ferrofluid shows wide pH/adsorbate applicability and strong ion selectivity in radionuclides absorption. Furthermore, it is anticipated to achieve maximum adsorption capacities for U(VI), Sr(II) and Co(II) as high as 331.5, 427.8 and 759.6 mg/g, respectively. With these characteristics, this ferrofluid outperforms other reported adsorbents. In conclusion, this work provides a practical and effective radioactive wastewater treatment strategy, and enlightens the development of materials for other applications facing the dilemma of incompatible stability and recyclability.

Establishment of Reference Interval and Aging Model of Homocysteine Using Real-World Data.

Objective: The level of Homocysteine (Hcy) in males is generally higher than that of females, but the same reference interval (RI) is often used in clinical practice. This study aims to establish a sex-specific RI of Hcy using five data mining algorithms and compare these results. Furthermore, age-related continuous RI was established in order to show the relationship between Hcy concentration distribution and age. Methods: A total of 20,801 individuals were included in the study and Tukey method was used to identify outliers in subgroups by sex and age. Multiple linear regression and standard deviation ratio (SDR) was used to determine whether the RI for Hcy needs to be divided by sex and age. Five algorithms including Hoffmann, Bhattacharya, expectation maximization (EM), kosmic and refineR were utilized to establish the RI of Hcy. Generalized Additive Models for Location Scale and Shape (GAMLSS) algorithm was used to determine the aging model of Hcy and calculate the age-related continuous RI. Results: RI of Hcy needed to be partitioned by sex (SDR = 0.735 > 0.375). RIs established by Hoffmann, Bhattacharya, EM (for females) and kosmic are all within the 95% CI of reference limits established by refine R. The Sex-specific aging model of Hcy showed that the upper limits of the RI of Hcy declined with age beginning at age of 18 and began to rise approximately after age of 40 for females and increased with age for males. Conclusion: The RI of Hcy needs to be partitioned by sex. The RIs established by the five data mining algorithms showed good consistency. The dynamic sex and age-specific model of Hcy showed the pattern of Hcy concentration with age and provide more personalized tools for clinical decisions.

UHPLC-MS/MS-Based Metabolomics and Clinical Phenotypes Analysis Reveal Broad-Scale Perturbations in Early Pregnancy Related to Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy, with adverse effects on both mother and fetus. The establishment of early diagnosis and risk assessment model is of great significance for preventing and reducing adverse outcomes of GDM. In this study, the broad-scale perturbations related to GDM were explored through the integration analysis of metabolic and clinical phenotypes. Maternal serum samples from the first trimester were collected for targeted metabolomics analysis by using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Statistical analysis was conducted based on the levels of the 184 metabolites and 76 clinical indicators from GDM women (n =60) and matched healthy controls (n =90). Metabolomics analysis revealed the down-regulation of fatty acid oxidation in the first trimester of GDM women, which was supposed to be related to the low serum level of dehydroepiandrosterone.While the significantly altered clinical phenotypes were mainly related to the increased risk of cardiovascular disease, abnormal iron metabolism, and inflammation. A phenotype panel established from the significantly changed serum indicators can be used for the early prediction of GDM, with the area under the receiver-operating characteristic curve (ROC) 0.83. High serum uric acid and C-reaction protein levels were risk factors for GDM independent of body mass indexes, with ORs 4.76 (95% CI: 2.08-10.90) and 3.10 (95% CI: 1.38-6.96), respectively. Predictive phenotype panel of GDM, together with the risk factors of GDM, will provide novel perspectives for the early clinical warning and diagnosis of GDM.