Performance verification of a biochemical detection system for hydrothorax and ascites and clinical diagnostic accuracy evaluation of exudate and tuberculous effusion.

Background: Lactate dehydrogenase (LDH), total protein (TP) and glucose (Glu) in pleural hydrothorax and ascites can be used in the diagnosis of exudate, and adenosine deaminase (ADA) can be used in the diagnosis of tuberculous effusion. However, the manufacturers do not claim that their biochemical reagents can be used to detect hydrothorax and ascites samples. Therefore, medical laboratories must conduct suitability studies on biochemical reagents for hydrothorax and ascites samples to comply with regulatory requirements for humor detection. This study aimed to verify the analytical performance and clinical diagnostic accuracy of the Mindray biochemical reagents, including LDH, TP, Glu and ADA, for hydrothorax and ascites. Methods: The repeatability, detection limits and reference intervals of Mindray biochemical reagents (LDH, TP, Glu, ADA) in detecting hydrothorax and ascites were determined. The comparison of different measurement procedures was performed. Meanwhile, the diagnostic accuracy of LDH, TP, Glu and ADA were assessed. Results: The quality control results of LDH, TP, Glu, and ADA were all under control. The repeatability coefficient of variation (%) of LDH, TP, Glu, and ADA were all less than 1%. The limits of blank of LDH, TP, Glu, and ADA were 0.33 U/L, 0.45 g/L, 0.00 mmol/L, and 0.04 U/L, respectively; the limits of detection were 1.57 U/L, 1.85 g/L, 0.05 mmol/L, and 0.12 U/L, respectively. Compared with the reference measurement program, the correlation coefficients of LDH, TP, Glu and ADA were 0.9931, 0.9983, 0.9996 and 0.9966, respectively; the regression equations were y=1.0082x-10.06, y=0.9965x-0.4732, y=0.9903x+0.0522 and y=1.0051x-0.0232, respectively. The reference intervals of LDH, TP, Glu, and ADA in hydrothorax and ascites were ≤198.39 U/L, ≤32.97 g/L, ≥5.03 mmol/L. and ≤11.00 U/L respectively. For differentiating between exudates and transudates, the area under the curve (AUC) of LDH, TP, and Glu were 0.913, 0.875, and 0.767, respectively; the AUC of ADA for the differential diagnosis of tuberculous and nontuberculous effusions was 0.876. Conclusions: The LDH, TP, Glu, and ADA assays were validated for use with the Mindray BS-2800 analyzer for hydrothorax and ascites evaluation. LDH, TP, and Glu in hydrothorax and ascites are applicable to the differential diagnosis of exudates and transudates; ADA in hydrothorax and ascites can be employed to differentiate and diagnose tuberculous and nontuberculous effusions.

Corrigendum: Non-alcoholic fatty liver disease is associated with aortic calcification: a cohort study with propensity score matching.

[This corrects the article DOI: 10.3389/fendo.2022.880683.].

Dietary Folate, Vitamin B6, and Vitamin B12 and Risk of Cardiovascular Diseases among Individuals with Type 2 Diabetes: A Case-Control Study.

BACKGROUND: Emerging evidence suggests that dietary one-carbon metabolism-related B-vitamins are associated with the reduced risk of cardiovascular disease (CVD) in the general population. However, only a few studies have assessed their associations in patients with type 2 diabetes (T2D). OBJECTIVE: This study aimed to assess the associations between the intake of three one-carbon metabolism-related B-vitamins (folate, vitamin B6, and vitamin B12) and CVD risk in Chinese patients with T2D. METHODS: A hospital-based case-control study of 419 patients with T2D and newly diagnosed CVD and 419 age- (±5 years) and sex-matched T2D-only controls was carried out in China. A validated 79-item semi-quantitative food-frequency questionnaire administered in face-to-face interviews was used to measure dietary B-vitamin intake. Conditional logistic regression was used to assess associations, which were tested by estimating odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Compared with the lowest quartile, the multivariable-adjusted ORs and 95% CIs for highest quartile were 0.32 (95% CI: 0.20, 0.52; p trend <0.001) for folate, 0.47 (95% CI: 0.30, 0.76; p trend = 0.002) for vitamin B6, and 1.02 (95% CI: 0.67, 1.55; p trend = 0.841) for vitamin B12. Consistent inverse associations were found for folate intake from eggs, vegetables, fruits, soy, and other foods but not for folate intake from grains. CONCLUSIONS: Findings suggest that the high consumption of folate and vitamin B6, but not that of vitamin B12, might be associated with the low risk of CVD in patients with T2D. This study suggests that dietary folate and vitamin B6 protect against CVD in patients with T2D.

Online prediction model for primary aldosteronism in patients with hypertension in Chinese population: A two-center retrospective study.

Background: The prevalence of primary aldosteronism (PA) varies from 5% to 20% in patients with hypertension but is largely underdiagnosed. Expanding screening for PA to all patients with hypertension to improve diagnostic efficiency is needed. A novel and portable prediction tool that can expand screening for PA is highly desirable. Methods: Clinical characteristics and laboratory data of 1,314 patients with hypertension were collected for modeling and randomly divided into a training cohort (919 of 1,314, 70%) and an internal validation cohort (395 of 1,314, 30%). Additionally, an external dataset (n = 285) was used for model validation. Machine learning algorithms were applied to develop a discriminant model. Sensitivity, specificity, and accuracy were used to evaluate the performance of the model. Results: Seven independent risk factors for predicting PA were identified, including age, sex, hypokalemia, serum sodium, serum sodium-to-potassium ratio, anion gap, and alkaline urine. The prediction model showed sufficient predictive accuracy, with area under the curve (AUC) values of 0.839 (95% CI: 0.81-0.87), 0.814 (95% CI: 0.77-0.86), and 0.839 (95% CI: 0.79-0.89) in the training set, internal validation, and external validation set, respectively. The calibration curves exhibited good agreement between the predictive risk of the model and the actual risk. An online prediction model was developed to make the model more portable to use. Conclusion: The online prediction model we constructed using conventional clinical characteristics and laboratory tests is portable and reliable. This allowed it to be widely used not only in the hospital but also in community health service centers and may help to improve the diagnostic efficiency of PA.

Simultaneous quantitation of 17 endogenous adrenal corticosteroid hormones in human plasma by UHPLC-MS/MS and their application in congenital adrenal hyperplasia screening.

Accurate investigation of adrenal hormone levels plays a vital role in pediatric endocrinology for the detection of steroid-related disorders. This study aims to develop a straightforward, sensitive UHPLC-MS/MS method to quantify 17 endogenous adrenal corticosteroid hormones in human plasma. These hormones are the main ingredients in the synthetic and metabolic pathways of adrenal corticosteroid hormones. Chromatographic separation was achieved on a C18 column before electrospray ionization triple-quadrupole mass spectrometry in multiple reaction monitoring mode with a run time of 7 min. The samples were extracted by liquid-liquid extraction and required no derivatization. Analytical performance was evaluated, including linearity, analytical sensitivity, accuracy, precision, and specificity. Plasma specimens from 32 congenital adrenal hyperplasia (CAH) patients and 30 healthy volunteers were analyzed to further reveal the diagnostic value of multiple steroid hormones in the synthetic and metabolic pathways of adrenal corticosteroid in CAH diagnosis. All hormones were effectively extracted and separated using our method. The method was essentially free from potential interference of isomers or structural analogues. The imprecisions were <10%. The lower limits of quantification varied from 0.05 to 15.0 ng/ml. Good linearity coefficients (r 2 > 0.998) were also obtained for most hormones in the required concentration range, except for 21-deoxycortisol (r 2 = 0.9967) and androstenediol (r 2 = 0.9952). The recoveries for the steroid hormones ranged from 91.7 to 109.8%. We developed the UHPLC-MS/MS method for the simultaneous measurement of steroid hormones. The results showed that measurement of steroid hormones simultaneously could improve the diagnostic efficiency of CAH.

Non-alcoholic Fatty Liver Disease Is Associated With Aortic Calcification: A Cohort Study With Propensity Score Matching.

Objectives: Non-alcoholic fatty liver disease (NAFLD) greatly affects cardiovascular disease, but evidence on the associations between NAFLD and markers of aortic calcification is limited. We aim to evaluate the association between NAFLD and aortic calcification in a cohort of Chinese adults using propensity score-matching (PSM) analysis. Methods: This prospective cohort study involved adults who underwent health-screening examinations from 2009 to 2016. NAFLD was diagnosed by abdominal ultrasonography at baseline, and aortic calcification was identified using a VCT LightSpeed 64 scanner. Analyses included Cox proportional-hazards regression analysis and PSM with predefined covariates (age, gender, marital and smoking status, and use of lipid-lowering drugs) to achieve a 1:1 balanced cohort. Results: Of the 6,047 eligible participants, 2,729 (45.13%) were diagnosed with NAFLD at baseline, with a median age of 49.0 years [interquartile range, 44.0-55.0]. We selected 2,339 pairs of participants with and without NAFLD at baseline for the PSM subpopulation. Compared with those without NAFLD, patients with NAFLD were at a higher risk of developing aortic calcification during follow-up; significant results were observed before and after matching, with the full-adjusted hazard ratios and corresponding 95% confidence intervals being 1.19 (1.02-1.38) and 1.18 (1.01-1.38), respectively (both p < 0.05). In subgroup analyses, no interaction was detected according to age, gender, smoking status, body mass index, total cholesterol, low-density lipoprotein cholesterol, use of lipid-lowering drugs, hypertension, or type 2 diabetes. Conclusions: NAFLD may be independently associated with aortic calcification. Further studies are warranted to elucidate the possible underlying mechanisms.

Sialic Acid as a Suitable Marker of Clinical Disease Activity in Patients with Crohn's Disease.

OBJECTIVE: Elevated serum levels of sialic acid (SA) have been verified in patients with various inflammatory conditions. The association between the Crohn's disease (CD) activity and serum SA has been insufficiently studied. MATERIALS AND METHODS: Serum SA concentrations were determined using an enzymatic colorimetric assay method, and the correlation of SA with the Harvey-Bradshaw Index (HBI) and other inflammation activity markers was evaluated using the Spearman correlation. The predictive value of SA in estimating CD disease activity was assessed using the receiver operating characteristic. RESULTS: The SA levels were positively correlated with HBI and C-reactive protein (CRP) levels. The correlation of SA with the HBI was superior to that of CRP with the HBI. The area under the curve for SA was higher than that for CRP, with an optimal cutoff value of 53.14 mg/dL for active CD. CONCLUSION: Serum SA correlates with the HBI score better and has better predictive value in monitoring CD disease activity than CRP or other inflammatory markers.

HDAC3 inhibition improves urinary-concentrating defect in hypokalaemia by promoting AQP2 transcription.

AIM: This study investigated whether enhanced histone acetylation, achieved by inhibiting histone deacetylases (HDACs), could prevent decreased aquaporin-2 (AQP2) expression during hypokalaemia. METHODS: Male Wistar rats were fed a potassium-free diet with or without 4-phenylbutyric acid (4-PBA) or the selective HDAC3 inhibitor RGFP966 for 4 days. Primary renal inner medullary collecting duct (IMCD) cells and immortalized mouse cortical collecting duct (mpkCCD) cells were cultured in potassium-deprivation medium with or without HDAC inhibitors. RESULTS: 4-PBA increased the levels of AQP2 mRNA and protein in the kidney inner medullae in hypokalaemic (HK) rats, which was associated with decreased urine output and increased urinary osmolality. The level of acetylated H3K27 (H3K27ac) protein was decreased in the inner medullae of HK rat kidneys; this decrease was mitigated by 4-PBA. The H3K27ac levels were decreased in IMCD and mpkCCD cells cultured in potassium-deprivation medium. Decreased H3K27ac in the Aqp2 promoter region was associated with reduced Aqp2 mRNA levels. HDAC3 protein expression was upregulated in mpkCCD and IMCD cells in response to potassium deprivation, and the binding of HDAC3 to the Aqp2 promoter was also increased. RGFP966 increased the levels of H3K27ac and AQP2 proteins and enhanced binding between H3K27ac and AQP2 in mpkCCD cells. Furthermore, RGFP966 reversed the hypokalaemia-induced downregulation of AQP2 and H3K27ac and alleviated polyuria in rats. RGFP966 increased interstitial osmolality in the kidney inner medullae of HK rats but did not affect urinary cAMP levels. CONCLUSION: HDAC inhibitors prevented the downregulation of AQP2 induced by potassium deprivation, probably by enhancing H3K27 acetylation.

An online alpha-thalassemia carrier discrimination model based on random forest and red blood cell parameters for low HbA2 cases.

BACKGROUND: Since screening of α-thalassemia carriers by low HbA2 has a low positive predictive value (PPV), the PPV was as low as 40.97% in our laboratory, other more effective screening methods need to be devised. This study aimed at developing a machine learning model by using red blood cell parameters to identify α-thalassemia carriers from low HbA2 patients. METHODS: Laboratory data of 1213 patients with low HbA2 used for modeling was randomly divided into the training set (849 of 1213, 70%) and the internal validation set (364 of 1213, 30%). In addition, an external data set (n = 399) was used for model validation. Fourteen machine learning methods were applied to construct a discriminant model. Performance was evaluated with accuracy, sensitivity, specificity, etc. and compared with 7 previously published discriminant function formulae. RESULTS: The optimal model was based on random forest with 5 clinical features. The PPV of the model was more than twice the PPV of HbA2, and the model had a high negative predictive value (NPV) at the same time. Compared with seven formulae in screening of α-thalassemia carriers, the model had a better accuracy (0.915), specificity (0.967), NPV (0.901), PPV (0.942) and area under the receiver operating characteristic curve (AUC, 0.948) in the independent test set. CONCLUSION: Use of a random forest-based model enables rapid discrimination of α-thalassemia carriers from low HbA2 cases.

Developing an ultra-performance liquid chromatography-tandem mass spectrometry for detecting aldosterone in human plasma.

BACKGROUND: Accurately measuring plasma aldosterone concentration is difficult but meaningful for primary aldosteronism (PA) diagnosis. METHODS: In this study, we developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for plasma aldosterone detection, evaluated its performance according to guidelines issued by CLSI, including detection limit, linearity, precision, and compared it with chemiluminescence immunoassay. Then, a reference range of plasma aldosterone in young people was established by using this method. RESULTS: The lower limit of quantitation (LOQ) was 10 pg/ml. The mean recovery rates of analyte added to serum were 100.07-102.05% in different concentrations. The linearity range was 20-2000 pg/ml. Inter-assay CVs were 2.20-3.97% at aldosterone concentrations of 65.66-854.75 pg/ml. The regression equation of UPLC-MS/MS (x) and chemiluminescence immunoassay (y) was y = 1.002x + 65.854 (r = 0.9456, n = 237). The reference range of plasma aldosterone detected by UPLC-MS/MS was 11.30-363.82 pg/ml in young people in South China, and there was no statistically significant difference in plasma aldosterone concentration between two genders. CONCLUSION: In conclusion, UPLC-MS/MS can rapidly and accurately detect plasma aldosterone and is appropriate for clinical application.

Serum creatinine as a biomarker for dystrophinopathy: a cross-sectional and longitudinal study.

BACKGROUND: Dystrophinopathy, a common neuromuscular disorder, includes Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Many researches are currently ongoing to develop curative approaches, which results in an urgent need for biomarkers of disease progression and treatment response. This study investigated whether the serum creatinine (SCRN) level can be used as a biomarker of disease progression in dystrophinopathy. METHODS: We enrolled 377 male patients with dystrophinopathy and 520 male non-dystrophinopathy controls in a cross-sectional study. From this cohort, 113 follow-up patients were enrolled in a longitudinal study. Patients' demographic information, motor function, muscle fatty infiltration, and muscle dystrophin levels were evaluated. We investigated correlations between these parameters and SCRN levels, and determined changes in SCRN levels with maturation and with motor function changes. RESULTS: Our results showed SCRN levels correlated with motor function (FDR < 0.001) and timed test results (FDR between < 0.001-0.012), as well as with muscle fatty infiltration (FDR < 0.001) and dystrophin levels (FDR = 0.015 and 0.001). SCRN levels increased with maturation in control individuals; it slowly increased with maturation in patients with BMD but decreased generally with maturation in patients with DMD. The longitudinal study further demonstrated that SCRN levels were associated with motor function. CONCLUSIONS: These findings indicated that the SCRN level is a promising biomarker for assessing disease progression in dystrophinopathy and could be used as a potential outcome measure in clinical trials.

GSK-3ß inhibitor TDZD-8 prevents reduction of aquaporin-1 expression via activating autophagy under renal ischemia reperfusion injury.

Renal ischemia/reperfusion (I/R) injury is a main cause of acute kidney injury (AKI). Aquaporin (AQP)-1 water channel in the kidney is critical for the maintenance of water homeostasis and the urinary concentrating ability. Increasing evidence supports an important role of autophagy in the pathogenesis of AKI induced by renal I/R. The purpose of the present study is to investigate whether activation of autophagy prevents downregulation of AQP1 protein induced by renal I/R and potential molecular mechanisms. Renal I/R induced consistently reduced protein expression of AQP1, 2, and 3, as well as sodium cotransporters Na+ -K+ -2Cl- cotransporter and α-Na,K-ATPase, which was associated with increased urine output and decreased creatinine clearance in rats. Renal I/R also suppressed autophagy and increased inflammatory responses in the kidney. 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), the glycogen synthase kinase-3ß inhibitor, ameliorated renal injury under I/R, activated autophagy and markedly increased expression of AQPs and sodium transporters in the kidney, which was associated with improved urine output and creatinine clearance in rats. Hypoxia/reoxygenation (H/R) induced suppression of autophagy and downregulation of AQP1 in murine inner medullary collecting duct 3 (IMCD3) cells, which was fully prevented by TDZD-8 treatment. Inhibition of autophagy by 3-methyladenine or Atg5 gene knockdown attenuated recovery of AQP1 protein expression induced by TDZD-8 in IMCD3 cells with H/R. Interleukin-1 beta (IL-1ß) decreased the abundance of AQP1 protein in IMCD3 cells. H/R induced increases in protein expression of nod-like receptor pyrin domain-containing 3 and IL-1ß, which was reversed by TDZD-8. In conclusion, TDZD-8 treatment prevented downregulation of AQP1 expression under renal I/R injury, likely via activating autophagy and decreasing IL-1ß production.

Prenatal Genetic Counseling in a Chinese Pregnant Woman With Rare Thalassemia: A Case Report.

Background: Prenatal genetic counseling can be difficult, especially when it is related to fetuses with a rare thalassemia. An intronic variant located far from obvious regulatory sequences in the HBB gene could be very difficult to evaluate as it may affect the mRNA processing or cause ß-thalassemia (ß-thal). In the present study, a Chinese pregnant woman with HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] in combination with α+-thalassemia was reported, which can assist in prenatal genetic counseling. Case Report: A 26-year-old pregnant woman presented at the obstetric clinic for a routine pregnancy check at 12 weeks of gestation. Red blood counts and high-performance liquid chromatography (HPLC) were consistent with clinical manifestations of anemia. Multiplex gap-polymerase chain (gap-PCR) displayed rightward deletion (-α3.7/αα). Direct DNA sequencing of the δ-globin gene showed no mutation. Sanger sequencing of the ß-globin gene showed a previously undescribed condition of double heterozygosity for HbJ-Bangkok and a very rare change in the second intron of the HBB gene [IVS-II-806(G>C), NM_000518.4, HBB: c.316-45G>C] that has not been previously reported in the HbVar database. Thus, a rare combination of α+-thal and a compound heterozygosity of HbJ-Bangkok and [IVS-II-806(G>C)] with α+-thal (-α3.7/αα) was finally diagnosed. Prenatal genetic counseling was made based on the genotype and phenotype analyses. Conclusion: This study enlarges the mutation spectrum of ß-globin gene and emphasizes DNA analysis in resolving unusual patterns in Hb analysis and the importance of sharing the observed rare undefined mutations and the possible interactions with known molecular defects, which can assist in prenatal genetic counseling.

Tubular Mas receptor mediates lipid-induced kidney injury.

Obesity-related kidney diseases are becoming serious health problems worldwide, yet the mechanism by which obesity causes kidney injury is not fully understood. The purpose of current study was to investigate the role of Mas receptor in lipid-induced kidney injury. In mice fed with high-fat diet (HFD), the protein abundance of markers of autophagy, endoplasmic reticulum stress (ER stress) and apoptosis was dramatically increased in the kidney cortex, which was markedly prevented by Mas deletion (Mas-/-) or Mas receptor antagonist A779. Palmitic acid (PA) induced persistently increased autophagy, ER stress, and apoptosis as well as mitochondrial injuries in primary cultured proximal tubular cells from wild type, but not from Mas-/- mice. In human proximal tubular HK2 cells, PA-induced autophagy and ER stress was aggravated by Mas agonists Ang (1-7) or AVE0991, but attenuated by A779 or Mas knockdown. Stimulation of Mas resulted in elevated intracellular calcium levels [Ca2+]i in HK2 cells treated with PA, whereas inhibition or knockdown of Mas decreased [Ca2+]i. Mitochondrial outer membrane located voltage-dependent anion channel (VDAC1) was markedly upregulated in HK2 cells treated with PA, which was associated with impaired mitochondrial morphology and depolarization. These were enhanced by AVE0991 and suppressed by A779 or Mas knockdown. Mas knockdown in HK2 cells prevented impaired interactions among VDAC1, autophagy adaptor P62, and ubiquitin, induced by PA, leading to a potential ubiquitination of VDAC1. In conclusion, Mas receptor-mediated lipid-induced impaired autophagy and ER stress in the kidney, likely contributing to tubular injuries in obesity-related kidney diseases.

High Efficiency and Problems of Chemiluminescence Assay-Detected Aldosterone-To-Renin Ratio in Practical Primary Aldosteronism Screening.

Primary aldosteronism is a main cause of secondary hypertension which can be effectively treated. The screening test for primary aldosteronism is benefit for minimizing damage to the patient. In the previous retrospective study, we obtained the optimal cutoff value of aldosterone-to-renin ratio detected by chemiluminescence assay, a newly developing method, and prompted its high efficiency in primary aldosteronism screening in upright position. In this study, we want to evaluate its efficiency in practical work. We used this ratio to continuously screen 238 patients, and 58 patients were finally diagnosed with primary aldosteronism. We found it had 86.13% accuracy rate in the upright position compared with the final clinical diagnosis. False negative and positive rates were 13.79% and 13.89%. Diagnostic sensitivity and specificity were 86.21% and 86.11%, which are slightly different from results in our previous study. False negative rate can be improved by combining the aldosterone-to-renin ratio with aldosterone concentration. We also found impaired glucose tolerance may be a reason for high false positive rate. Besides, chemiluminescence assay may be interfered in aldosterone detection. Although it has some shortcomings, chemiluminescence assay-detected aldosterone-to-renin ratio is a highly effective index for screening primary aldosteronism in practice.

Inhibition of IL-1ß by Aliskiren Improved Renal AQP2 Expression and Urinary Concentration Defect in Ureteral Obstruction and Release.

We previously demonstrated that ureteral obstruction is associated with a urinary concentrating defect and reduced expression of renal aquaporins (AQPs), in which the renin-angiotensin system (RAS) may play an important role. The aims of the present study were to examine whether the renin inhibitor aliskiren could prevent the reduction in AQP expression and improve the urinary concentrating capacity in mice with bilateral ureteral obstruction (BUO) and BUO release. BUO was performed for 24 h, and BUO release was performed for 1 (B-R1D) or 3 days (B-R3D) with or without aliskiren treatment. Aliskiren prevented polyuria and decreased urine osmolality induced by B-R3D. In mice with BUO and BUO release, aliskiren attenuated the reduction in AQP2 protein and mRNA expression in the obstructed kidneys. B-R3D increased the protein expression of NLRP3 inflammasome components ASC, caspase-1, and interleukin-1ß in the obstructed kidneys, which was markedly prevented by aliskiren. Moreover, the NF-κB inhibitor Bay 11-7082 blocked NLRP3 inflammasome activation and attenuated the decrease in AQP2 protein expression in primary cultured rat inner medullary collecting duct cells treated with angiotensin II. These results indicate that the renin inhibitor aliskiren increases water channel AQP2 expression at least partially by suppressing NLRP3 inflammasome activation in the obstructed kidneys of mice with BUO and BUO release.

Clinical value of interferon-γ release assay in the diagnosis of active tuberculosis.

Sensitivity and specificity of the interferon-γ release test for active tuberculosis screening were evaluated. Due to the high-test cost of imported IGRAs, QFT-GIT and T-SPOT.TB, we applied a cheaper domestic TB-IGRA which was approved in China recently. We recruited 740 patients and performed tuberculosis interferon release test (IGRAs), detection of Mycobacterium tuberculosis IgG antibody (TB-IgG) and tuberculin skin test (TST). The sensitivity of the three methods are 90.8, 40.0 and 75.45%, with specificity of 76.62, 74.47 and 72.27%. The area under the ROC curve according to the value of T-N detected by IGRAs was 0.878 (95% CI, 0.839-0.917), with the area under the curve for the diagnosis of active pulmonary tuberculosis and extrapulmonary tuberculosis being 0.839 and 0.841 respectively. The interferon-γ release test seems to be superior to TST and TB-IgG as a screening tool for the detection of active tuberculosis in China.

Serum magnesium and the prevalence of peripheral artery disease: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND AIMS: Peripheral arterial disease (PAD) is a clinical manifestation of extracoronary atherosclerosis. Many risk factors are involved in the process of PAD, but the association between serum magnesium (Mg) and PAD is not clear. Our study aimed to investigate whether serum Mg is associated with PAD incidence. METHODS: A total of 13,826 participants (aged 40-64 years) in the Atherosclerosis Risk in Communities (ARIC) study (1987-1989) without prior PAD were included in the final analysis. Serum Mg levels were measured at visits 1 and 2. PAD was defined as an ankle brachial index less than 0.9, or hospitalization with a PAD diagnosis. Cox regression was used to calculate hazard ratios (HRs) for incidence of PAD and serum Mg. RESULTS: During a median follow-up of 24.4 years, 1364 (48.4% female) PAD events were observed. After multiple adjustment, participants in the lowest (≤1.4 mEq/L) category of serum Mg compared with the highest (≥1.8 mEq/L) ones were at higher PAD risk (HR: 1.3; 95% confidence interval (CI): 1.06-1.58) (p value = 0.004). The HRs for PAD in 1.5, 1.6 and 1.7 mEq/L of serum Mg were 1.29 (95% CI: 1.08-1.54), 1.05 (95% CI: 0.89-1.24), and 1.0 (95% CI: 0.85-1.18), respectively. CONCLUSIONS: Low serum Mg was independently associated with an increased prevalence of PAD in the large population-based study; further studies are needed to confirm our findings.

High efficiency of the aldosterone-to-renin ratio in precisely detecting primary aldosteronism.

The aldosterone-to-renin ratio (ARR) is extensively used for primary aldosteronism detection. Chemiluminescence immune assay (CLIA) is newly applied in aldosterone and renin detection for calculating the aldosterone-to-renin ratio. The performance of new ARR in aldosteronism detection is poorly evaluated. We aim to estimate the diagnostic value of this new aldosterone-to-renin ratio by highly standardized and clinically based protocol. Four hundred and forty-two patients were enrolled in our retrospective study. They went to the first affiliated hospital of Sun Yat-sen University with difficult-to-control hypertension. Primary aldosteronism diagnosis was based on clinical criteria, including a saline infusion test and other necessary inspections. ARR was calculated from plasma aldosterone and renin measured by CLIA. The cutoff value was determined and the diagnostic value was evaluated. The cutoff value of ARR for primary aldosteronism diagnosis was 28.3, with a sensitivity of 87.6%, specificity of 100%, negative-predictive value of 96.4%, and positive-predictive value of 100%. Then, we found that Age was weakly correlated with ARR. The cutoff values of ARR for primary aldosteronism diagnosis in 26-45-, 46-65-, and 66-85-year-old patients were, respectively, 29.45, 27.95, and 28.4, with sensitivities of 87.5%, 87.7%, and 87.5%, specificities of 100% for all, negative-predictive values of 97.7%, 94.3%, and 96.3%, and positive-predictive values of 100% for all. ARR generated by CLIA is a good diagnostic test for primary aldosteronism without making a false-positive diagnosis. Although ARR is correlated with age, ARR cutoff values for different ages are not more efficient than that for total sample in primary aldosteronism diagnosis.

Combination of Chymostatin and Aliskiren attenuates ER stress induced by lipid overload in kidney tubular cells.

BACKGROUND: Lipotoxicity plays an important role in the pathogenesis of kidney injury. Our previous study demonstrated that activation of local renin-angiotensin system (RAS) was involved in saturated free fatty acids palmitic acid (PA)-induced tubular cell injuries. The current study aims to investigate whether suppression of RAS by combination of direct renin inhibitor aliskiren and noncanonical RAS pathway chymase inhibitor chymostatin attenuates PA or cholesterol induced-endoplasmic reticulum stress (ER stress) and apopotosis in cultured human proximal tubular HK2 cells. METHODS: HK2 cells were treated with saturated fatty acid PA (0.6 mM) for 24 h or cholesterol (10 µg/ml) for 6d with or without chymostatin and/or aliskiren. Expressions of the ER stress associated proteins and apoptosis markers were detected by western blotting. The mRNA levels of RAS components were measured by real-time qPCR. RESULTS: Combination treatment of chymostatin and aliskiren markedly suppressed PA or cholesterol-induced ER stress, as reflected by increased BiP, IRE1α, phosphorylated-eIF2α and ATF4 as well as proapoptotic transcription factor CHOP. The ratio of Bax/Bcl-2 and cleaved caspase-3, two markers of apoptosis were upregulated by PA or cholesterol treatment. PA treatment was also associated with increased levels of angiotensinogen and angiotensin type 1 receptor (AT1R) mRNA expression. Combination treatment of chymostatin and aliskiren markedly suppressed PA or cholesterol-induced ER stress and apoptosis. The protective effect of two inhibitors was also observed in primary cultured cortical tubular cells treated with PA. In contrast, chymostatin and/or aliskiren failed to prevent ER stress induced by tunicamycin. CONCLUSIONS: These results suggested that combination treatment of chymostatin and aliskiren attenuates lipid-induced renal tubular cell injury, likely through suppressing activation of intracellular RAS.