Efficacy of Opportunistic Screening with Chest CT in Identifying Osteoporosis and Osteopenia in Patients with T2DM.

Purpose: To explore the validity of the thoracic spine Hounsfield Unit (HU) measured by chest computed tomography (CT) for opportunistic screening of diabetic osteoporosis. The current study attempted to establish a diagnostic threshold for thoracic spine HU in a type 2 diabetes mellitus (T2DM) population with osteoporosis. Patients and Methods: The current study retrospectively included 334 patients with T2DM. They underwent chest CT and Dual-energy X-ray (DXA) between August 2021 and January 2022 in our hospital. HU values were measured on the resulting chest CT images at thoracic spine 11 and 12 to construct regions of interest. All patients were grouped according to the lowest T-value of DXA examination: osteoporosis, osteopenia and normal bone density. HU values were compared with T-values in each group of patients, and receiver operating characteristics curves were plotted to calculate diagnostic thresholds as well as sensitivity and specificity. Results: There was a strong correlation between the HU values of chest CT and the T-values of DXA (p < 0.01). The sensitivity for osteoporosis was 88.7% for T11 attenuation≤ 98 HU and the specificity for osteoporosis was 87.5% for T12 attenuation ≤ 117HU; the specificity for normal BMD was 85.4% for T11 attenuation ≥ 147 HU and 82% for T12 attenuation ≥ 146 HU. Conclusion: Chest CT can be used to screen patients with T2DM for opportunistic osteoporosis and help determine if they need DXA screening. The current study suggests that when the HU threshold of T11 ≤ 98/T12 ≤ 117, patients may need further osteoporosis screening.

Opportunistic prediction of osteoporosis in patients with degenerative lumbar diseases: a simplified T12 vertebral bone quality approach.

BACKGROUND: Osteoporosis is one of the risk factors for screw loosening after lumbar fusion. However, the probability of preoperative osteoporosis screening in patients with lumbar degenerative disease is low. Therefore, the aim of this study was to investigate whether a simplified vertebral bone quality (VBQ) score based on T12 T1-MRI could opportunistically predict osteoporosis in patients with degenerative lumbar spine diseases. METHODS: We retrospectively analyzed cases treated for lumbar degenerative diseases at a single institution between August 2021 and June 2022. The patients were divided into three groups by the lowest T-score: osteoporosis group, osteopenia group, and normal bone mineral density (BMD) group. The signal intensity based on the T12 vertebral body divided by the signal intensity of the cerebrospinal fluid was calculated to obtain the simplified VBQ score, as well as the CT-based T12HU value and the traditional L1-4VBQ score. Various statistical analyses were used to compare VBQ, HU and DEXA, and the optimal T12VBQ threshold for predicting osteoporosis was obtained by plotting the receiver operating curve (ROC) analysis. RESULTS: Total of 166 patients were included in this study. There was a statistically significant difference in T12VBQ scores between the three groups (p < 0.001). Pearson correlation showed that there was a moderate correlation between T12VBQ and T-score (r=-0.406, p < 0.001). The AUC value of T12VBQ, which distinguishes between normal and low BMD, was 0.756, and the optimal diagnostic threshold was 2.94. The AUC value of T12VBQ, which distinguishes osteoporosis from non-osteoporosis, was 0.634, and the optimal diagnostic threshold was 3.18. CONCLUSION: T12VBQ can be used as an effective opportunistic screening method for osteoporosis in patients with lumbar degenerative diseases. It can be used as a supplement to the evaluation of DEXA and preoperative evaluation. TRIAL REGISTRATION: retrospectively registered number:1502-009-644; retrospectively registered number date:27 oct 2022.

Boron toxicity induced specific changes of cell ultrastructure and architecture of components in leaf center and tip of trifoliate orange [Poncirus trifoliata (L.) Raf.].

The distribution of boron (B) in leaves is far from uniform, and tolerance to B toxicity should be varied in different portions of an entire leaf. Here, according to the order and degree of leaf chlorosis, a whole leaf blade of trifoliate orange [Poncirus trifoliata (L.) Raf.] rootstock was divided into two segments-leaf tip and leaf center, and transmission electron microscope (TEM) and fourier transform infrared spectroscopy (FTIR) were used to obtain more detailed information on the cell ultrastructure and component architecture of the two leaf segments under B toxicity. Results revealed that B toxicity led to alterations in pectin network crosslinking structure of leaf tip and destruction of cell wall integrity. Moreover, B toxicity altered protein structure and decreased protein content, while increased carbohydrate content in the two leaf segments, especially in leaf tip. Excess B supply reduced the cellulose content in leaf tip but increased in leaf center. TEM micrographs exhibited chloroplast disintegration and plastoglobulus accumulation in cells of two different leaf sections of B-toxicity plants, with less pronounced changes in leaf center. Furthermore, B toxicity only induced accumulation of starch grains in cells of leaf center. Overall results indicated that the B-toxic-induced biochemical changes of the cell ultrastructure and component architecture greatly differed in leaf tip and center. This study facilitates a better understanding of structural changes in different leaf portions of P. trifoliata under B toxicity stress and provides new ideas for further research on other elements in different plant leaf portions.

Spectrum of SLC20A2, PDGFRB, PDGFB, and XPR1 mutations in a large cohort of patients with primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder with four causative genes (SLC20A2, PDGFRB, PDGFB, and XPR1) that have been identified. Here, we aim to describe the mutational spectrum of four causative genes in a series of 226 unrelated Chinese PFBC patients. Mutations in four causative genes were detected in 16.8% (38/226) of PFBC patients. SLC20A2 mutations accounted for 14.2% (32/226) of all patients. Mutations in the other three genes were relatively rare, accounting for 0.9% (2/226) of all patients, respectively. Clinically, 44.8% of genetically confirmed patients (probands and relatives) were considered symptomatic. The most frequent symptoms were chronic headache, followed by movement disorders and vertigo. Moreover, the total calcification score was significantly higher in the symptomatic group compared to the asymptomatic group. Functionally, we observed impaired phosphate transport induced by seven novel missense mutations in SLC20A2 and two novel mutations in XPR1. The mutation p.D164Y in XPR1 might result in low protein expression through an enhanced proteasome pathway. In conclusion, our study further confirms that mutations in SLC20A2 are the major cause of PFBC and provides additional evidence for the crucial roles of phosphate transport impairment in the pathogenies of PFBC.

Different metabolite profile and metabolic pathway with leaves and roots in response to boron deficiency at the initial stage of citrus rootstock growth.

Boron (B) is a microelement required for higher plants, and B deficiency has serious negative effect on metabolic processes. We concentrated on the changes in metabolite profiles of trifoliate orange leaves and roots as a consequence of B deficiency at the initial stage of growth by gas chromatography-mass spectrometry (GC-MS)-based metabolomics. Enlargement and browning of root tips were observed in B-deficient plants, while any obvious symptom was not recorded in the leaves after 30 days of B deprivation. The distinct patterns of alterations in metabolites observed in leaves and roots due to B deficiency suggest the presence of specific organ responses to B starvation. The accumulation of soluble sugars was occurred in leaves, which may be attributed to down-regulated pentose phosphate pathway (PPP) and amino acid biosynthesis under B deficiency, while the amount of most amino acids in roots was increased, indicating that the effects of B deficiency on amino acids metabolism in trifoliate orange may be a consequence of disruptions in root tissues and decreased protein biosynthesis. Several important products of shikimate pathway were also significantly affected by B deficiency, which may be related to abnormal growth of roots induced by B deficiency. Conclusively, our results revealed a global perspective of the discriminative metabolism responses appearing between B-deprived leaves and roots and provided new insight into the relationship between B deficiency symptom in roots and the altered amino acids profiling and shikimate pathway induced by B deficiency during seedling establishment.

Development and validation of an HPLC-MS/MS method to determine clopidogrel in human plasma.

A quantitative method for clopidogrel using online-SPE tandem LC-MS/MS was developed and fully validated according to the well-established FDA guidelines. The method achieves adequate sensitivity for pharmacokinetic studies, with lower limit of quantifications (LLOQs) as low as 10 pg/mL. Chromatographic separations were performed on reversed phase columns Kromasil Eternity-2.5-C18-UHPLC for both methods. Positive electrospray ionization in multiple reaction monitoring (MRM) mode was employed for signal detection and a deuterated analogue (clopidogrel-d 4) was used as internal standard (IS). Adjustments in sample preparation, including introduction of an online-SPE system proved to be the most effective method to solve the analyte back-conversion in clinical samples. Pooled clinical samples (two levels) were prepared and successfully used as real-sample quality control (QC) in the validation of back-conversion testing under different conditions. The result showed that the real samples were stable in room temperature for 24 h. Linearity, precision, extraction recovery, matrix effect on spiked QC samples and stability tests on both spiked QCs and real sample QCs stored in different conditions met the acceptance criteria. This online-SPE method was successfully applied to a bioequivalence study of 75 mg single dose clopidogrel tablets in 48 healthy male subjects.

Determination of Sodium Tanshinone IIA Sulfonate in human plasma by LC-MS/MS and its application to a clinical pharmacokinetic study.

An assay based on protein precipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated for the quantitative analysis of Sodium Tanshinone IIA Sulfonate (STS) in human plasma. After the addition of dehydroepiandrosterone-D5-3-sulfate sodium salt (DHEAS-D5) as internal standard (IS) and formic acid, plasma samples were prepared by one-step protein precipitation with a mixture of acetonitrile and methanol. Isocratic mobile phase consisted of 0.4 mmol/L ammonium formate buffer (16 ppm formic acid)/acetonitrile (40/60, v/v) on a XSELECT™ HSS T3 column. Detection was performed on a triple-quadrupole mass spectrometer utilizing an electrospray ionization (ESI) interface operating in positive ion and selected reaction monitoring (SRM) mode with the precursor to product ion transitions m/z 373.3→357.1 for STS and m/z 373.0→97.8 for the IS. Calibration curves of STS in human plasma were linear (r=0.9957-0.9998) over the concentration range of 2-1000 ng/mL with acceptable accuracy and precision. The lower limit of quantification in human plasma was 2 ng/mL. The validated LC-MS/MS method has been successfully applied to a pharmacokinetic study of STS in Chinese healthy male volunteers.