Accelerated 3D MR neurography of the brachial plexus using deep learning-constrained compressed sensing.

OBJECTIVES: To explore the use of deep learning-constrained compressed sensing (DLCS) in improving image quality and acquisition time for 3D MRI of the brachial plexus. METHODS: Fifty-four participants who underwent contrast-enhanced imaging and forty-one participants who underwent unenhanced imaging were included. Sensitivity encoding with an acceleration of 2 × 2 (SENSE4x), CS with an acceleration of 4 (CS4x), and DLCS with acceleration of 4 (DLCS4x) and 8 (DLCS8x) were used for MRI of the brachial plexus. Apparent signal-to-noise ratios (aSNRs), apparent contrast-to-noise ratios (aCNRs), and qualitative scores on a 4-point scale were evaluated and compared by ANOVA and the Friedman test. Interobserver agreement was evaluated by calculating the intraclass correlation coefficients. RESULTS: DLCS4x achieved higher aSNR and aCNR than SENSE4x, CS4x, and DLCS8x (all p < 0.05). For the root segment of the brachial plexus, no statistically significant differences in the qualitative scores were found among the four sequences. For the trunk segment, DLCS4x had higher scores than SENSE4x (p = 0.04) in the contrast-enhanced group and had higher scores than SENSE4x and DLCS8x in the unenhanced group (all p < 0.05). For the divisions, cords, and branches, DLCS4x had higher scores than SENSE4x, CS4x, and DLCS8x (all p ≤ 0.01). No overt difference was found among SENSE4x, CS4x, and DLCS8x in any segment of the brachial plexus (all p > 0.05). CONCLUSIONS: In three-dimensional MRI for the brachial plexus, DLCS4x can improve image quality compared with SENSE4x and CS4x, and DLCS8x can maintain the image quality compared to SENSE4x and CS4x. CLINICAL RELEVANCE STATEMENT: Deep learning-constrained compressed sensing can improve the image quality or accelerate acquisition of 3D MRI of the brachial plexus, which should be benefit in evaluating the brachial plexus and its branches in clinical practice. KEY POINTS: •Deep learning-constrained compressed sensing showed higher aSNR, aCNR, and qualitative scores for the brachial plexus than SENSE and CS at the same acceleration factor with similar scanning time. •Deep learning-constrained compressed sensing at acceleration factor of 8 had comparable aSNR, aCNR, and qualitative scores to SENSE4x and CS4x with approximately half the examination time. •Deep learning-constrained compressed sensing may be helpful in clinical practice for improving image quality and acquisition time in three-dimensional MRI of the brachial plexus.

Inhibition of endogenous hydrogen sulfide production suppresses the growth of nasopharyngeal carcinoma cells.

Hydrogen sulfide (H2 S) has been widely recognized as one of gasotransmitters. Endogenous H2 S plays a crucial role in the progression of cancer. However, the effect of endogenous H2 S on the development of nasopharyngeal carcinoma (NPC) is still unknown. In this study, aminooxyacetic acid (AOAA, an inhibitor of cystathionine-ß-synthase), dl-propargylglycine (PAG, an inhibitor of cystathionine-γ-lyase), and l-aspartic acid (l-Asp, an inhibitor of 3-mercaptopyruvate sulfurtransferase) were adopted to detect the role of endogenous H2 S in NPC growth. The results indicated that the combine (PAG + AOAA + l-Asp) group had higher inhibitory effect on the growth of NPC cells than the PAG, AOAA, and l-Asp groups. There were similar trends in the levels of apoptosis and reactive oxygen species (ROS). In addition, the combine group exhibited lower levels of phospho (p)-extracellular signal-regulated protein kinase but higher expressions of p-p38 and p-c-Jun N-terminal kinase than those in the AOAA, PAG, and l-Asp groups. Furthermore, the combine group exerted more potent inhibitory effect on NPC xenograft tumor growth without obvious toxicity. In summary, suppression of endogenous H2 S generation could dramatically inhibit NPC growth via the ROS/mitogen-activated protein kinase pathway. Endogenous H2 S may be a novel therapeutic target in human NPC cells. Effective inhibitors for H2 S-producing enzymes could be designed and developed for NPC treatment.

Two-dimensional Be2Al and Be2Ga monolayer: anti-van't Hoff/Le Bel planar hexacoordinate bonding and superconductivity.

Because of the electron deficiency of boron, a triangular network with planar hexacoordination is the most common structural and bonding property for isolated boron clusters and two-dimensional (2D) boron sheets. However, this network is a rule-breaking structure and bonding case for all other main-group elements. Herein, the Be2M (M = Al and Ga) 2D monolayer with P6/mmm space group was found to be the lowest-energy structure with planar hexacoordinate Be/Al/Ga motifs. More interestingly, Be2Al and Be2Ga were observed to be intrinsic phonon-mediated superconductors with a superconducting critical temperature (Tc) of 5.9 and 3.6 K, respectively, where compressive strain could further enhance their Tc. The high thermochemical and kinetic stability of Be2M make a promising candidate for experimental realization, considering its high cohesive energy, absence of soft phonon modes, and good resistance to high temperature. Moreover, the feasibility of directly growing Be2M on the electride Ca2N substrate was further demonstrated, where its intriguing electronic and superconducting properties were well maintained in comparison with the freestanding monolayer. The Be2M monolayer with rule-breaking planar hexacoordinate motifs firmly pushes the ultimate connection of the "anti-van't Hoff/Le Bel" structure with promising physical properties.

Analysis of Trio Half Sibling Testing.

OBJECTIVES: To establish an analytical method for half sibling testing involving common three relatives' participation. METHODS: Based on the half sibling testing scenarios with the known biological mother, grandfather or uncle, and two unidentified controversial half siblings participating, two opposing hypotheses were set. Lineage reconstruction according to Mendel's law of heredity was carried out, and the calculation formula of the half sibling kinship index was derived. Verification of actual cases was carried out and the results were compared with duo half sibling testing. RESULTS: In the scenarios of the known biological mother, grandfather and uncle participating in half sibling testing, the kinship calculation formulae of 54, 91 and 99 genotype combinations for kinship index calculation were deduced respectively. The actual cases showed higher kinship indexes in trio half sibling testing compared with duo half sibling testing. CONCLUSIONS: It is beneficial to obtain more genetic information for family reconstruction and improvement of the strength of genetic evidence for half sibling testing by adding known relatives.

Hitting the Bull's Eye: Stable HeBeOH+ Complex.

It is now known that the heavier noble gases (Ng=Ar-Rn) show some varying degrees of reactivity with a gradual increase in reactivity along Ar-Rn. However, because of their very small size and very high ionization potential, helium and neon are the hardest targets to crack. Although few neon complexes are isolated at very low temperatures, helium needs very extreme situations like very high pressure. Here, we find that protonated BeO, BeOH+ can bind helium and neon spontaneously at room temperature. Therefore, extreme conditions like very low temperature and/or high pressure will not be required for their experimental isolation. The Ng-Be bond strength is very high for their heavier homologs and the bond strength shows a gradual increase from He to Rn. Moreover, the Ng-Be attractive energy is almost exclusively originated from the orbital interaction which is composed of one Ng(s/pσ )→BeOH+ σ-donation and two weaker Ng(pπ )→BeOH+ π-donations, except for helium. Helium uses its low-lying vacant 2p orbitals to accept π-electron density from BeOH+ . Previously, such electron-accepting ability of helium was used to explain a somewhat stronger helium bond than neon for neutral complexes. However, the present results indicate that such π-back donations are too weak in nature to decide any energetic trend between helium and neon.

Automatic machine learning based on native T1 mapping can identify myocardial fibrosis in patients with hypertrophic cardiomyopathy.

OBJECTIVES: To investigate the feasibility of automatic machine learning (autoML) based on native T1 mapping to predict late gadolinium enhancement (LGE) status in hypertrophic cardiomyopathy (HCM). METHODS: Ninety-one HCM patients and 44 healthy controls who underwent cardiovascular MRI were enrolled. The native T1 maps of HCM patients were classified as LGE ( +) or LGE (-) based on location-matched LGE images. An autoML pipeline was implemented using the tree-based pipeline optimization tool (TPOT) for 3 binary classifications: LGE ( +) and LGE (-), LGE (-) and control, and HCM and control. TPOT modeling was repeated 10 times to obtain the optimal model for each classification. The diagnostic performance of the best models by slice and by case was evaluated using sensitivity, specificity, accuracy, and microaveraged area under the curve (AUC). RESULTS: Ten prediction models were generated by TPOT for each of the 3 binary classifications. The diagnostic accuracy obtained with the best pipeline in detecting LGE status in the testing cohort of HCM patients was 0.80 by slice and 0.79 by case. In addition, the TPOT model also showed discriminability between LGE (-) patients and control (accuracy: 0.77 by slice; 0.78 by case) and for all HCM patients and controls (accuracy: 0.88 for both). CONCLUSIONS: Native T1 map analysis based on autoML correlates with LGE ( +) or (-) status. The TPOT machine learning algorithm could be a promising method for predicting myocardial fibrosis, as reflected by the presence of LGE in HCM patients without the need for late contrast-enhanced MRI sequences. KEY POINTS: • The tree-based pipeline optimization tool (TPOT) is a machine learning algorithm that could help predict late gadolinium enhancement (LGE) status in patients with hypertrophic cardiomyopathy. • The TPOT could serve as an adjuvant method to detect LGE by using information from native T1 maps, thus avoiding the need for contrast agent. • The TPOT also detects native T1 map alterations in LGE-negative patients with hypertrophic cardiomyopathy.

[Early Assessment of Myocardial Fibrosis of Hypertrophic Cardiomyopathy with Native-T1-Mapping-Based Deep Learning: A Preliminary Study].

OBJECTIVE: To explore the diagnostic performance of deep learning (DL) model in early detection of the interstitial myocardial fibrosis using native T1 maps of hypertrophic cardiomyopathy (HCM) without late gadolinium enhancement (LGE). METHODS: Sixty HCM patients and 44 healthy volunteers who underwent cardiac magnetic resonance were enrolled in this study. Each native T1 map was labeled according to its LGE status. Then, native T1 maps of LGE (-) and those of the controls were preprocessed and entered in the SE-ResNext-50 model as the matrix for the DL model for training, validation and testing. RESULTS: A total of 241 native T1 maps were entered in the SE-ResNext-50 model. The model achieved a specificity of 0.87, sensitivity of 0.79, and area under curve ( AUC) of 0.83 ( P<0.05) in distinguishing native T1 maps of LGE (-) from those of the controls in the testing set. CONCLUSION: The DL model based on SE-ResNext-50 could be used for identifying native T1 maps of LGE (-) with relatively high accuracy. It is a promising approach for early detection of myocardial fibrosis in HCM without the use of contrast agent.

Persistent Hematuria and Kidney Disease Progression in IgA Nephropathy: A Cohort Study.

RATIONALE & OBJECTIVE: Hematuria is the most typical presentation of immunoglobulin A nephropathy (IgAN); however, its role in disease progression is still controversial. This study aimed to evaluate the association of hematuria and progression of IgAN. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A cohort of 1,333 patients with IgAN treated at a Chinese referral hospital with a median follow-up of 45 months. PREDICTORS: Microhematuria was evaluated in fresh urine using a fully automated urine particle analyzer (automated method) and urine sediment examination by a skilled examiner (manual method). Hematuria was characterized as a time-varying attribute; namely, average hematuria level was calculated for every 6-month period for each patient during follow-up. Remission was defined as average red blood cell count ≤5/high-power field (manual method) or ≤28 red blood cells/µL (automated method) during the first 6 months of follow-up. OUTCOMES: Composite event of 50% decline in estimated glomerular filtration rate or development of kidney failure. ANALYTICAL APPROACH: Multivariable cause-specific hazards models to analyze the relationship between hematuria and the composite kidney disease progression event. RESULTS: Time-varying hematuria during follow-up was an independent risk factor for the composite kidney disease progression event (HR, 1.46; 95% CI, 1.13-1.87; P = 0.003). Hematuria remission during the 6 months after diagnosis was associated with a significantly lower rate of the composite kidney disease progression event (HR, 0.41; 95% CI, 0.28-0.61; P < 0.001). A significant interaction was detected between remission of proteinuria and remission of hematuria during the first 6 months (P < 0.001). The association between remission of hematuria and kidney disease progression was detectable (HR, 0.46; 95% CI, 0.32-0.68) within the subpopulation with persistent proteinuria (protein excretion > 1.0 g/d during the first 6 months), but not among patients whose proteinuria had remitted (HR, 0.64; 95% CI, 0.31-1.29; P = 0.2). The 2 techniques for hematuria evaluation were strongly and significantly linearly correlated (r = 0.948; P < 0.001), and results using these 2 methods were consistent. LIMITATIONS: A single-center retrospective study. Proportional hazards regression incorporating time-varying covariates may create time-varying confounding. The predictive value of reductions in hematuria was not directly evaluated. CONCLUSIONS: Level of hematuria was independently associated with kidney disease progression, whereas hematuria remission was associated with improved kidney outcomes in IgAN among patients with persistent proteinuria. Additionally, to monitor IgAN progression, automated methods to evaluate hematuria hold promise as a replacement for manual evaluation of urinary sediment.

Associations of Sex Steroids With Changes in Calcaneal Quantitative Ultrasound Measurements: A Longitudinal Study in Chinese Male Adolescents.

This 2-year longitudinal study aimed to detect the associations of sex steroids, sex hormone-binding globulin with bone parameters and the changes thereof in Chinese male adolescents. A total of 642 male students aged 12-16 years from a secondary school in Jiangmen, China, were included. Total testosterone (T), total oestradiol (E2), and sex hormone-binding globulin were measured by chemiluminescence immunoassay. The bioavailable T (BioT) and E2 (BioE2) were calculated. The speed of sound, broadband ultrasound attenuation, and stiffness index of the right heel were measured by Sahara Clinical Bone Sonometer at both baseline and 2-year follow-up. The confounding effects of age, height, weight, pubertal stage, physical activity, energy-adjusted dietary calcium intake, and dietary vitamin D intake were adjusted. The baseline value of each bone parameter was also adjusted in the longitudinal analysis. Results showed that total T and BioT were positively associated with bone parameters and changes in them (ß = 0.076-0.115, p < 0.05). A threshold effect of BioT on broadband ultrasound attenuation, stiffness index and their changes were also observed. Positive associations between BioT and bone mass gain were observed only in individuals with BioT levels <240.0 ng/dl (ß = 0.088-0.131, p < 0.05). Moreover, total E2 or BioE2 were found to be inversely associated with speed of sound and its change (ß = -0.109 to -0.077, p < 0.05). This study supported that in Chinese male adolescents, serum T was a positive predictor for bone formation with a threshold effect, and E2 could have influence on the changes in bone architecture during puberty. These findings may improve the understanding of the effects of sex steroids on the acceleration of bone formation in male adolescents and provide useful information for the prediction model establishment of peak bone mass.

Diagnostic test accuracy of new generation tympanic thermometry in children under different cutoffs: a systematic review and meta-analysis.

BACKGROUND: The infrared tympanic thermometer (IRTT) is a popular method for temperature screening in children, but it has been debated for the low accuracy and reproducibility compared with other measurements. This study was aimed to identify and quantify studies reporting the diagnostic accuracy of the new generation IRTT in children and to compare the sensitivity and specificity of IRTT under different cutoffs and give the optimal cutoff. METHODS: Articles were derived from a systematic search in PubMed, Web of Science Core Collection, and Embase, and were assessed for internal validity by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The figure of risk of bias was created by Review Manager 5.3 and data were synthesized by MetaDisc 1.4. RESULTS: Twelve diagnostic studies, involving 4639 pediatric patients, were included. The cut-offs varied from 37.0 °C to 38.0 °C among these studies. The cut-off 37.8 °C was with the highest sROC AUC (0.97) and Youden Index (0.83) and was deemed to be the optimal cutoff. CONCLUSION: The optimal cutoff for infrared tympanic thermometers is 37.8 °C. New Generation Tympanic Thermometry is with high diagnostic accuracy in pediatric patients and can be an alternative for fever screening in children.

Associations between estimated glomerular filtration rate and cardiac biomarkers.

BACKGROUND: Chronic kidney disease (CKD) is associated with an increased cardiovascular disease (CVD) mortality risk. Elevation of cardiac biomarkers in patients with renal dysfunction is ambiguous in the diagnosis of CVD. The purpose of this study was to investigate the associations between estimated glomerular filtration rate (eGFR) and cardiac biomarkers, and the influence of renal dysfunction on the cardiac biomarkers. METHODS: We examined the cross-sectional associations of eGFR with cardiac troponin I (cTnI), creatine kinase (CK), CK-MB, lactic dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), and brain natriuretic peptide (BNP) in 812 adults and 215 child. Spearman correlation and logistic regression analysis were performed to evaluate the associations. RESULTS: For adults, lower eGFR CKD-EPI had significantly higher cTnI, CK-MB, LDH, HBDH, and BNP. There were negative correlations between eGFRCKD-EPI and cTnI, CK-MB, LDH, HBDH, and BNP. After adjustment for potential confounders, as compared with eGFRCKD-EPI  ≥ 90 mL/min/1.73 m2 , eGFRCKD-EPI  < 60 mL/min/1.73 m2 remained associated with a 2.83 (1.08-7.41) [ratio (95% CI)] times higher cTnI and a 6.50 (2.32-18.22) [ratio (95% CI)] times higher HBDH. For child, lower eGFRSchwartz had significant higher CK and CK-MB. There were negative correlations between eGFRSchwartz and CK, and eGFRSchwartz and CK-MB. After adjustment for potential confounders, as compared with eGFRSchwartz  ≥ 90 mL/min/1.73 m2 , eGFRSchwartz  < 90 mL/min/1.73 m2 revealed no significant higher CVD biomarkers. CONCLUSION: Reduced eGFR is associated with elevated cTnI and HBDH among adults without clinically evident CVD, but not child.

Disordered intestinal microbes are associated with the activity of Systemic Lupus Erythematosus.

Intestinal dysbiosis is implicated in Systemic Lupus Erythematosus (SLE). However, the evidence of gut microbiome changes in SLE is limited, and the association of changed gut microbiome with the activity of SLE, as well as its functional relevance with SLE still remains unknown. Here, we sequenced 16S rRNA amplicon on fecal samples from 40 SLE patients (19 active patients, 21 remissive patients), 20 disease controls (Rheumatoid Arthritis (RA) patients), and 22 healthy controls (HCs), and investigated the association of functional categories with taxonomic composition by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). We demonstrated SLE patients, particularly the active patients, had significant dysbiosis in gut microbiota with reduced bacterial diversity and biased community constitutions. Amongst the disordered microbiota, the genera Streptococcus, Campylobacter, Veillonella, the species anginosus and dispar, were positively correlated with lupus activity, while the genus Bifidobacterium was negatively associated with the disease activity. PICRUSt analysis showed metabolic pathways were different between SLE and HCs, and also between active and remissive SLE patients. Moreover, we revealed that a random forest model could distinguish SLE from RA and HCs (area under the curve (AUC) = 0.792), and another random forest model could well predict the activity of SLE patients (AUC = 0.811). In summary, SLE patients, especially the active patients, show an apparent dysbiosis in gut microbiota and its related metabolic pathways. Amongst the disordered microflora, four genera and two species are associated with lupus activity. Furthermore, the random forest models are able to diagnose SLE and predict disease activity.

Factors Influencing Aspirin Hyporesponsiveness in Elderly Chinese Patients.

BACKGROUND Aspirin hyporesponsiveness increases the risk of ischemic events. Therefore, it is important to investigate the factors influencing aspirin hyporesponsiveness. MATERIAL AND METHODS Patients aged 60 years or older who did not take aspirin before enrollment were included, with aspirin 100 mg/day administered after enrollment. The arachidonic acid-induced platelet aggregation rate (Ara) was measured by light transmission assay to evaluate aspirin responsiveness. Patients with Ara in the upper quartile after taking aspirin were assigned to the aspirin hyporesponsive group (Ara-Q4). RESULTS A total of 292 elderly patients were included. The median value of Ara after taking aspirin was 5.87% (interquartile range 3.86-10.04%). Compared with the aspirin non-hyporesponsive group (Ara-Q1-3, Ara ≤10.04%, n=220), the level of uric acid (UA) (341.30 µmol/L vs. 299.10 µmol/L, p=0.027) and the ratios of ß-blockers (9.72% vs. 2.27%, p=0.015) and diuretics (6.94% vs. 1.36%, p=0.036) were higher in the aspirin hyporesponsive group (Ara-Q4, Ara >10.04%, n=72). After multivariate adjustment, the results demonstrated baseline Ara (odds ratio [OR]: 1.030, 95% confidence interval [CI]: 1.004-1.056, p=0.021), UA level (OR: 1.003, 95% CI: 1.000-1.006, p=0.038), and ß-blockers use (OR: 5.487, 95% CI: 1.515-19.870, p=0.010) were independently and positively associated with aspirin hyporesponsiveness. CONCLUSIONS This study found that baseline Ara, UA level, and ß-blockers use were independently and positively associated with aspirin hyporesponsiveness in elderly Chinese patients, which needs to be validated in large-scale studies.

LncRNA PLAC2 down-regulates RPL36 expression and blocks cell cycle progression in glioma through a mechanism involving STAT1.

Current glioma therapies allow in situ delivery of cytotoxic drugs to the tumour; however, gliomas show early recurrence due to their highly proliferative character. Long non-coding (lnc)RNAs play critical roles in tumorigenesis by controlling cell proliferation and cycling. However, the mechanism of action of lncRNAs in glioma development remains unclear. Here, we report that the lncRNA PLAC2 induces cell cycle arrest by targeting ribosomal protein (RP)L36 in glioma. RPL36 promoted cell proliferation and G1/S cell cycle progression. Mass spectrometry analysis revealed that signal transducer and activator of transcription (STAT)1 interacted with both lncRNA PLAC2 and the RPL36 promoter. We also found that the nucleus PLAC2 bind with STAT1 and interact with RPL36 promoters but the cytoplasmic lncRNA PLAC2 inhibited STAT1 nuclear transfer, thereby decreasing RP36 expression, inhibiting cell proliferation and inducing cell cycle arrest. These results provide evidence for a novel cell cycle regulatory network in glioma comprising the lncRNA PLAC2 along with STAT1 and RPL36 that can serve as a therapeutic target for glioma treatment.

The RopGEF2-ROP7/ROP2 Pathway Activated by phyB Suppresses Red Light-Induced Stomatal Opening.

Circadian rhythm of stomatal aperture is mainly regulated by light/darkness. Blue and red light induce stomatal opening through different mechanisms that are mediated by special receptors. ROP2, a member of Rho GTPase family in Arabidopsis (Arabidopsisthaliana), has been found to negatively regulate light-induced stomatal opening. However, the upstream guanine nucleotide exchange factor (GEF) RopGEFs have not been revealed, and it is unclear which photoreceptor is required for the action of RopGEFs-ROPs. Here, we showed that RopGEF2 acted as a negative regulator in phytochrome B (phyB)-mediated red light-induced stomatal opening. Meanwhile, ROP7, another member of ROP family, acting redundantly with ROP2, was regulated by RopGEF2 in this process. RopGEF2 interacted with ROP7 and ROP2 and enhanced their intrinsic nucleotide exchange rates. Furthermore, the direct interactions between phyB and RopGEF2 were detected in vitro and in plants, and phyB enhanced the GEF activity of RopGEF2 toward both ROP7 and ROP2 under light. In addition, RopGEF4 functioned redundantly with RopGEF2 in red light-induced stomatal opening by activating both ROP7 and ROP2, and RopGEF2/RopGEF4 acted genetically downstream of phyB; however, the GEF activity of RopGEF4 was not directly enhanced by phyB. These results revealed that red light-activated phyB enhances the GEF activities of RopGEF2 and RopGEF4 directly or indirectly, and then activate both ROP7 and ROP2 in guard cells. The negative mechanism triggered by phyB prevents the excessive stomatal opening under red light.

SOX2-mediated inhibition of miR-223 contributes to STIM1 activation in phenylephrine-induced hypertrophic cardiomyocytes.

Stromal interaction molecule 1 (STIM1) is the key molecule responsible for store-operated Ca2+ entry (SOCE). Numerous studies have demonstrated that STIM1 levels appeared to be enhanced during cardiac hypertrophy. However, the mechanism underlining this process remains to be clarified. In this study, phenylephrine (PE) was employed to establish a model of hypertrophic neonatal rat cardiomyocytes (HNRCs) in vitro, and low expression of primary and mature miR-223 was detected in PE-induced HNRCs. Our results have revealed that downregulation of miR-223 by PE contributed to the increase of STIM1, which in turn induced cardiac hypertrophy. As expected, overexpression of miR-223 could prevent the increase in cell surface and reduce the mRNA levels of ANF and BNP in cardiomyocytes. To address the mechanism triggering downregulation of miR-223 under PE, we demonstrated that PE-induced inhibition of GSK-3ß activity led to the activation of ß-catenin, which initiates the transcription of SOX2. Increased expression of SOX2 occupied the promoter region of primary miR-223 and suppressed its transcription. Therefore, miR-223 appears to be a promising candidate for inhibiting cardiomyocyte hypertrophy, and miR-223/STIM1 axis might be one of interesting targets for the clinical treatment of hypertrophy.

Evaluation of genetic parameters of 23 autosomal STR loci in a Southern Chinese Han population.

AIM: To evaluate the 23 autosomal short tandem repeat (STR) loci included in GoldenEye™ 25 A kit using forensic human identification and paternity testing. SUBJECTS AND METHODS: In total, 3751 unrelated individuals from the Southern Chinese Han population were genotyped with the 5-dye GoldenEye™ 25 A multiplex amplification system. PCR products were separated using arrayed capillary electrophoresis. Allele frequencies and forensic parameters for the 23 autosomal STR loci were statistically analysed. RESULTS: A total of 344 alleles were observed, with corresponding allelic frequencies ranging from 0.0001-0.5519 for the 23 STR loci. No significant deviation from the Hardy-Weinberg equilibrium and linkage disequilibrium was observed. The combined power of discrimination (CPD) was 1-1.6290 × 10-28 and the combined power of exclusion (CPE) was 0.999 999 999 89 and 0.999 999 286 93 for trio and duo cases, respectively. From 3865 meioses, 87 mutation events were discovered. The mutation rate varied from 0-0.00285 for each locus. One-step mutation accounted for 94.25% of total mutations. The ratio of paternal vs maternal mutation was 3.76:1.13 kinds of n/(n + 1) heterozygote genotypes were observed. CONCLUSIONS: The results show that 23 STR loci of GoldenEye™ 25 A kit are highly polymorphic in the Southern Chinese Han population, indicating the kit is suitable for forensic application.

Assessment of Glycated Albumin as a Useful Indicator for Renal Dysfunction in Diabetic and Nondiabetic Population.

BACKGROUND: Glycated albumin (GA) reflects serum glucose of the preceding 2 - 3 weeks and plays an important role in diabetes mellitus (DM). This study aimed at investigating whether GA can assess renal dysfunction in population. METHODS: 3818 individuals attending physical examination were enrolled in this cross-sectional study and divided into five groups: healthy controls, impaired fasting glucose, DM without renal complications, DM with albuminuria, and nondiabetic chronic kidney disease patients. All analyses were conducted using the subjects with both fasting venous blood and morning urine samples. RESULTS: Among all groups, mean GA, hemoglobin A1c, fasting plasma glucose, and serum creatinine were the highest and estimated glomerular filtration rate (eGFR) was the lowest in DM with albuminuria group. When eGFR was 90 - 105 mL/minute/1.73 m2 or mildly decreased to 60 - 90 mL/minute/1.73 m2, GA increased significantly with elevating albumin-to-creatinine ratio (ACR) from 0 - 10 mg/g to 10 - 30 mg/g to > 30 mg/g (p < 0.001 and p < 0.001). GA increased further when eGFR decreased moderately to severely as a result of renal function continuing to deteriorate (eGFR ≤ 60 mL/minute/1.73 m2).When ACR ≤ 30 mg/g and eGFR ≤ 60 mL/minute/ 1.73 m2, more than 50% subjects were DM patients and had significantly higher GA levels than other subjects with eGFR > 105 mL/minute/1.73 m2. After adjusting demographics, every 5% rise of GA levels showed a 1.778fold increased risk in all subjects (adjusted odds ratio [OR], 1.778; 95% confidence interval [CI], 1.373 - 2.302; p < 0.001) and 1.737-fold risk in DM subjects (adjusted OR, 1.737; 95% CI, 1.221 - 2.471; p = 0.002) for occurrence of ACR > 30mg/g in contrast to ACR ≤ 30 mg/g. Compared to eGFR > 90 mL/minute/1.73 m2, 5% rise of GA levels showed a 1.482-fold risk for eGFR 60 - 90 mL/minute/1.73 m2 (adjusted OR, 1.482; 95% CI, 1.112 - 1.975; p = 0.007) and a 1.996-fold risk for eGFR ≤ 60 mL/minute/1.73 m2 (adjusted OR, 1.996; 95% CI, 1.366 - 2.916; p < 0.001). CONCLUSIONS: Increased GA serves as a risk marker for renal dysfunction. GA combined with eGFR and ACR can reflect renal function changes in population.

The Reference Intervals for Serum C-Terminal Agrin Fragment in Healthy Individuals and as a Biomarker for Renal Function in Kidney Transplant Recipients.

BACKGROUND: C-terminal agrin fragment (CAF) has been shown to be a promising new biomarker for kidney function. The aim of this study was to verify the reference intervals for CAF in Chinese healthy adults and to assess the efficiency of CAF for monitoring renal function after transplantation. METHODS: Serum samples were collected from 200 healthy adult subjects and 60 living donor kidney recipients before and on day 1, day 2 and at 6 months after transplantation. We measured serum CAF, creatinine, cystatin C and NGAL concentrations at each time. Estimated glomerular filtration rate (eGFR) was evaluated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Reference intervals for CAF were determined at 2.5th and 97.5th percentiles. RESULTS: Serum CAF concentrations were observed to be higher in females of old age groups while no significant differences were discovered in males between age groups. There were significant gender-related differences in CAF in old age groups (50-64 and ≥65 years). Serum CAF correlated positively with serum creatinine, cystatin C and negatively with eGFR on day 1, day 2 and at 6 months after kidney transplantation. CAF and NGAL fell rapidly into the normal range on the second postoperative day, prior to creatinine and cystatin C. CONCLUSIONS: This study verified the reference intervals for serum CAF. CAF could be a potential new biomarker for kidney function monitoring.

Analysis of 24 Y-STR haplotype data in a Chinese Han population from Guangdong Province.

In this study, we investigated the genetic polymorphisms of 24 Y-chromosomal short tandem repeat (Y-STR) loci in 885 unrelated Chinese Han male individuals from Guangdong Province, using a domestic AGCU Y24 STR kit. A total of 878 different haplotypes were observed at the 24 Y-STR loci; among them, 871 haplotypes were unique and 7 haplotypes occurred twice. The overall haplotype diversity was 0.99998 and the discrimination capacity was 99.2%. The gene diversity values ranged from 0.4354 at DYS438 to 0.9606 at DYS385a/b. Population relationships between the Guangdong Han population and seven other published Chinese populations were evaluated by Rst values and visualized in a two multi-dimensional scaling plot. The results showed the 24 Y-STR loci are highly polymorphic in Guangdong Han population and of great value in forensic application.