SERS-electrochemical dual-mode detection of microRNA on same interface assisted by exonuclease III signal transformation.

Dual-mode sensing has attracted more attentions which provide more accurate and reliable approach of cancer-related biomarkers. Herein, we developed a novel SERS/electrochemical dual-mode biosensor for miRNA 21 detection based on Exo III-assisted signal transformation. Firstly, the Au NPs were deposited on electrode as SERS substrate and Mn3O4/S4(DNA signal strand) was modified on Au NPs/S5 by the DNA strands S5-S4 pairing principle as hydrogen peroxide catalyst, leading to an obviously high DPV electrical signal without Raman signal. Subsequently, the presence of miRNA 21 will activate the Mn3O4/S4 to be decomposed under exonuclease III-assisted process, then the S3' chains modified with Raman molecular Cy3(Cy3-S3') is continuously connected to the Au NPs/S5 by DNA stands S5-S3' pairing principle, leading to the Raman signal response and DPV signal reduction. The biosensor shows good linear calibration curves of both SERS and electrochemical sensing modes with the detection limit of 3.98 × 10-3 nM and 6.89 × 10-5 nM, respectively. This work finds an ingenious mode for dual detection of microRNA on a same interface, which opens a new strategy for SERS and electrochemical analysis.

MRI-based Vertebral Bone Quality Score for Osteoporosis Screening Based on Different Osteoporotic Diagnostic Criteria Using DXA and QCT.

In this study, we aim to evaluate the correlation between T score measured by dual X-ray absorptiometry (DXA), volumetric bone mineral density (vBMD) derived from quantitative computed tomography (QCT) and MRI-based vertebral bone quality (VBQ), explore the diagnostic performance of VBQ in osteoporosis and determine the recognition value of VBQ in osteoporotic fracture in a relatively large cohort of elderly patients scheduled to undergo spinal surgery. A total of 260 patients were enrolled in the study. DXA and QCT were used to evaluate osteoporotic status. We calculated the lumbar VBQ score, analyzed the correlation between T score, vBMD and VBQ, and explored whether VBQ was an influential factor of bone quality and fracture by binary logistic regression as well as the diagnostic performance of VBQ in osteoporosis and fracture by ROC curve. VBQ was negatively correlated with vBMD and T score. (r = - 0.487 vs. r = - 0.220). The VBQ score was a risk factor for osteoporosis under the QCT diagnostic criteria (OR = 2.245, 95% CI 1.456-3.460) and osteoporotic fractures (OR = 1.496, 95% CI 1.097-2.040). It exhibited superior discriminant performance for osteoporosis diagnosed by QCT, with a cutoff value of 3.70 and an AUC of 0.7354. Its cutoff value for osteoporotic fractures was 3.72, and its AUC was 0.6717. In a cohort of elderly patients scheduled to undergo spinal surgery, the VBQ score was more strongly associated with vBMD than the T score and could identify patients with osteoporosis and corresponding vertebral compression fracture (VCF).

Assessment of bone density using the 1.5 T or 3.0 T MRI-based vertebral bone quality score in older patients undergoing spine surgery: does field strength matter?

BACKGROUND CONTEXT: Recently published studies have revealed a correlation between MRI-based vertebral bone quality (VBQ) score and bone mineral density (BMD) measured using dual X-ray absorptiometry (DXA) or quantitative computed tomography (QCT). However, no studies have determined if differences in field strength (1.5 vs 3.0 T) could affect the comparability of the VBQ score among different individuals. PURPOSE: To compare the VBQ score obtained from 1.5 T and 3.0 T MRI (VBQ1.5T vs VBQ3.0T) in patients undergoing spine surgery and assess the predictive performance of VBQ for osteoporosis and osteoporotic vertebral fracture (VCF). DESIGN: A nested case‒control study based on an ongoing prospective cohort study of patients undergoing spine surgery. PATIENT SAMPLE: All older patients (men aged >60 years and postmenopausal women) with available DXA, QCT and MR images within 1 month were included. OUTCOME MEASURES: VBQ score, DXA T-score, and QCT derived vBMD. METHODS: The osteoporotic classifications recommended by the World Health Organization and American College of Radiology were used to categorize the DXA T-score and QCT-derived BMD, respectively. For each patient, the VBQ score was calculated using T1-weighted MR images. Correlation analysis between VBQ and DXA/QCT was performed. Receiver operating characteristic (ROC) curve analysis, including determination of the area under the curve (AUC), was performed to assess the predictive performance of VBQ for osteoporosis. RESULTS: A total of 452 patients (98 men aged >60 years and 354 postmenopausal women) were included in the analysis. Across different BMD categories, the correlation coefficients between the VBQ score and BMD ranged from -0.211 to -0.511, and the VBQ1.5T score and QCT BMD demonstrated the strongest correlation. The VBQ score was a significant classifier of osteoporosis detected by either DXA or QCT, with VBQ1.5T showing the highest discriminative power for QCT-osteoporosis (AUC=0.744, 95% CI=0.685-0.803). In ROC analysis, the VBQ1.5T threshold values ranged from 3.705 to 3.835 with a sensitivity between 48% and 55.6% and a specificity between 70.8% and 74.8%, while the VBQ3.0T threshold values ranged from 2.59 to 2.605 with a sensitivity between 57.6% and 67.1% and a specificity between 67.8% and 69.7%. CONCLUSIONS: VBQ1.5T exhibited better discriminability between patients with and without osteoporosis than VBQ3.0T. Considering the non-negligible difference in osteoporosis diagnosis threshold values between the VBQ1.5T and VBQ3.0T scores, it is essential to clearly distinguish the magnetic field strength when assessing the VBQ score.

Quantitative CT screening improved lumbar BMD evaluation in older patients compared to dual-energy X-ray absorptiometry.

BACKGROUND: Robust evidence on whether diagnostic discordance exists between lumbar osteoporosis detected by quantitative computed tomography (QCT) vs. dual-energy X-ray absorptiometry (DXA) is still lacking. In this study involving a relatively large prospective cohort of older men (aged > 60 years) and postmenopausal women, we assessed lumbar QCT-derived volumetric bone mineral density (vBMD) and DXA-derived area BMD and evaluated their predictive performance for prevalent vertebral fracture (VF). METHODS: A total of 501 patients who underwent spinal surgery from September 2020 to September 2022 were enrolled. The criteria recommended by the American College of Radiology and the World Health Organization were used for lumbar osteoporosis diagnosis. The osteoporosis detection rates between QCT and DXA were compared. QCT-vBMD was plotted against the DXA T score, and the line of best fit was calculated based on linear regression. Multivariate logistic regression was used to analyze the associations between risk factors and VF. Receiver operating characteristic curve analysis was performed, and the corresponding area under the curve (AUC) was calculated. RESULTS: QCT screening showed that 60.7% of patients had osteoporosis, whereas DXA screening showed that 50.7% of patients had osteoporosis. Diagnoses were concordant for 325 (64.9%) patients. In all, 205 patients suffered a VF of at least one anatomic level. Of these, 84.4% (173/205) were diagnosed with osteoporosis by QCT, while only 73.2% (150/205) were diagnosed by DXA. Multivariate logistic regression showed that osteoporosis detected by QCT exhibited a stronger relationship with VF than that detected by DXA (unadjusted OR, 6.81 vs. 5.04; adjusted OR, 3.44 vs. 2.66). For discrimination between patients with and without VF, QCT-vBMD (AUC = 0.802) showed better performance than DXA T score (AUC = 0.76). CONCLUSION: In older patients undergoing spinal surgery, QCT-vBMD is more helpful than DXA in terms of osteoporosis detection rate and prediction of patients with prevalent VFs.

Discordance in lumbar bone mineral density measurements by quantitative computed tomography and dual-energy X-ray absorptiometry in postmenopausal women: a prospective comparative study.

BACKGROUND CONTEXT: Level-specific lumbar bone mineral density (BMD) evaluation of a single vertebral body can provide useful surgical planning and osteoporosis management information. Previous comparative studies have primarily focused on detecting spinal osteoporosis but not at specific levels. PURPOSE: To compare the detection rate of lumbar osteoporosis between quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA); to explore and analyze the distribution models of QCT-derived BMD and DXA T-score at the specific levels; and to evaluate the diagnostic accuracy of level-specific BMD thresholds for the prediction of osteoporotic vertebral compression fracture (OVCF) in postmenopausal women. STUDY DESIGN/SETTING: A comparative analysis of prospectively collected data comparing QCT-derived BMD with DXA T-score. PATIENT SAMPLE: A total of 296 postmenopausal women who were referred to the spine service of a single academic institution were enrolled. OUTCOME MEASURES: QCT-derived BMD and DXA T-score at specific levels, with or without osteoporotic vertebral compression fracture. METHODS: Postmenopausal women who underwent QCT and DXA within a week of admission from May 2019 to June 2022 were enrolled. The diagnostic criteria for osteoporosis recommended by the World Health Organization and the American College of Radiology were used for lumbar osteoporotic diagnosis. To evaluate differences in lumbar BMD measurements at specific levels, a threshold of T score=-2.5 and QCT-derived BMD = 80 mg/cm3 were used to categorize level-specific lumbar BMD into low and high BMD. Disagreements in BMD categorization between DXA and QCT were classified as a minor or major discordance based on the definition by Woodson. Data between QCT and DXA were visualized in a stacked bar plot and analyzed. Correlations between DXA and QCT at the specific levels were evaluated using Pearson's linear correlation and scatter plots. Curve fitting of BMD distribution, receiver operating characteristic (ROC) and area under the curve (AUC) for each single vertebral level was performed. RESULTS: Of the 296 patients, QCT diagnosed 61.1% as osteoporosis, 30.4% as osteopenia and 8.4% as normal. For those screened with DXA, 54.1% of the patients had osteoporosis, 29.4% had osteopenia and 16.6% had normal BMD. Diagnoses were concordant for 194 (65.5%) patients. Of the other 102 discordant patients, 5 (1.7%) were major and 97 (32.8%) were minor. Significant correlations in level-specific BMD between DXA and QCT were observed (p<.001), with Pearson's correlation coefficients ranging from 0.662 to 0.728. The correlation strength was in the order of L1 > L2 > L3 > L4. The low BMD detection rate for QCT was significantly higher than that for DXA at the L3 and L4 levels (65% vs. 47.9% and 68.1% vs 43.7, respectively, p<.001). Patients with OVCF showed significantly lower QCT-derived BMD (47.2 mg/cm3 vs. 83.2 mg/cm3, p<.001) and T-score (-3.39 vs. -1.98, p<.001) than those without OVCF. Among these patients, 82.8% (101/122) were diagnosed with osteoporosis by QCT measurement, while only 74.6% (91/122) were diagnosed by DXA. For discrimination between patients with and without OVCF, QCT-derived BMD showed better diagnosed performance (AUC range from 0.769 to 0.801) than DXA T-score (AUC range from 0.696 to 0.753). CONCLUSION: QCT provided a more accurate evaluation of lumbar osteoporosis than DXA. The QCT-derived BMD measurements at a specific lumbar level have a high diagnostic performance for OVCF.

Novel Pedicle Navigator Based on Micro Inertial Navigation System (MINS) and Bioelectric Impedance Analysis (BIA) to Facilitate Pedicle Screw Placement in Spine Surgery: Study in a Porcine Model.

STUDY DESIGN: A porcine model. OBJECTIVE: The study aims to design a novel pedicle navigator based on micro-inertial navigation system (MINS) and bioelectrical impedance analysis (BIA) to assist place pedicle screw placement and validate the utility of the system in enhancing pedicle screw placement. SUMMARY OF BACKGROUND DATA: The incidence of pedicle screw malpositioning in complicated spinal surgery is still high.Procedures such as computed tomography image-guided navigation, and robot-assisted surgery have been used to improve the precision of pedicle screw placement, but it remains an unmet clinical need. METHODS: The miniaturized integrated framework containing MINS was mounted inside the hollow handle of the pedicle finder. The inner core was complemented by a high-intensity electrode for measuring bioelectric impedance. Twelve healthy male Wuzhishan minipigs of similar age and weight were used in this experiment and randomized to the MINS-BIA or freehand (FH) group. Pedicle screw placement was determined according to the modified Gertzbein-Robbins grading system on computed tomography images. An impedance detected by probe equal to the baseline value for soft tissue was defined as cortical bone perforation. RESULTS: A total of 216 screws were placed in 12 minipigs. There were 15 pedicle breaches in the navigator group and 31 in the FH group; the detection rates of these breaches were 14 of 15 (93.3%) and 25 of 31 (80.6%), respectively, with a statistically significant difference between groups. The mean offsets between the planned and postoperatively measured tilt angles of the screw trajectory were 4.5° ± 5.5° in the axial plane and 4.8° ± 3.3° in the sagittal plane with the navigator system and 7.0° ± 5.1° and 7.7° ± 4.7°, respectively, with the FH technique; the differences were statistically significant. CONCLUSION: A novel and portable navigator based on MINS and BIA could be beneficial for improving or maintaining accuracy while reducing overall radiation exposure.

Thermosensitive liposomes with higher phase transition temperature for targeted drug delivery to tumor.

Thermosensitive liposomes (TSL) in combination with local hyperthermia (HT) represent a promising tool for tumor specific drug delivery. The objective of the study was to investigate the influence of phase transition temperature (Tm) on the properties of TSL. High temperature triggered TSL (HTSL), low temperature triggered TSL (LTSL) and non-TSL (NTSL) were prepared and temperature sensitive release properties were extensively compared in different media. Mouse plasma was determined to have similar effect on the release profiles compared to human plasma, in which complete release were obtained at 38 °C and 40 °C for LTSL and HTSL, respectively. The temperature at which complete release achieved was found to be obviously lower than Tm. Brucine, an antitumor alkaloid, was encapsulated into different TSLs. After HT treatment, the viabilities of SMMC 7721 cells were determined to be 21.3±3.8% and 16.8±3.3% for 127 µM brucine LTSL and HTSL, respectively. Treating the tumor-bearing mice with LTSL, HTSL and NTSL led to significantly increased brucine uptake in the heated tumor site compared to the brucine solution group by 2.30, 3.80 and 2.26-fold, respectively. The results of this study suggested that Tm of TSL should be increased to obtain improved drug delivery efficiency to tumor.

Brucine-loaded liposomes composed of HSPC and DPPC at different ratios: in vitro and in vivo evaluation.

OBJECTIVE: The objective of this study is to test the hypothesis that the phase transition temperature (T(m)), the main property of liposomes, can be easily controlled by changing the molar ratio of hydrogenated soy phosphatidylcholine (HSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphacholine (DPPC) after drug encapsulation. MATERIALS AND METHODS: Brucine, an antitumor alkaloid, was encapsulated into the liposomes with different HSPC/DPPC compositions. The T(m)s of the brucine-loaded liposomes (BLs) were determined by differential scanning calorimetry (DSC). Then the physicochemical properties and pharmacokinetics of the BLs with different HSPC/DPPC compositions were investigated and compared. RESULTS: The results of DSC revealed that HSPC and DPPC can combine into one phase. The findings of molecular modeling study suggested that HSPC interacts with DPPC via electrostatic interaction. The molar ratio of HSPC/DPPC influenced the sizes of BLs but had little effect on the entrapment efficiency (EE). The stability of BLs was improved with the increase of the HSPC ratios, especially with the presence of plasma. Following i.v. administration, it was found that AUC values of BLs in vivo were directly related to the HSPC/DPPC ratios of BLs, namely the T(m)s of BLs. DISCUSSION: The behavior of liposomes, especially in vivo pharmacokinetic behavior, can be controlled by the modification of T(m). CONCLUSION: The characterization of BLs in vitro and in vivo had demonstrated that the Tm could be flexibly modified for liposomes composed of both HSPC and DPPC. Using HSPC/DPPC composition may be an efficient strategy to control the T(m), thus control the in vivo pharmacokinetic behavior, of BLs.

[Study on preparation and thermosensitive release property of composite phospholipid liposomes containing total alkaloids from Strychnos nux-vomica].

To prepare composite phospholipid liposomes containing total alkaloids of Strychnos nux-vomica with hydrogenated soybean phosphatidylcholine (HSPC) and 1, 2-dipalmitoyl-sn-glycero-3-phosphacholine (DPPC), and compare with normal DPPC thermosensitive liposomes for thermosensitive release property. Total alkaloids were extracted from S. nux-vomica with the impregnation method and further purified. Liposomes containing total alkaloids, thermosensitive liposomes and conventional thermosensitive liposomes without thermosensitive release property were prepared by ammonium sulfate transmembrane gradients and stealth liposome technique. Their encapsulation efficiency (EE), grain size, zeta potential and drug release behavior were compared. Their EEs and zeta potentials were almost identical; but the grain sizes of composite phospholipid liposomes and thermosensitive liposomes were significantly smaller than conventional liposomes. After comparing release behaviors of the three liposomes at 37, 43 degrees C, we found that the release of composite phospholipid liposomes was significantly lower than that of thermosensitive liposomes at 37 degrees C, but higher than that of thermosensitive liposomes at 43 degrees C. Meanwhile, conventional liposomes, with a very high phase-transition temperature, showed only slight release behavior at both temperatures. The study results showed that composite phospholipid liposomes had a better thermosensitive release behavior when the dosage of lysophosphatidic was reduced by 2. 5 times.

[Determination and comparison of plasma protein binding rate of alkaloids from seed of Strychnou nux-vomica].

OBJECTIVE: To determine the plasma protein binding rates of brucine and strychnine in total alkaloids from the seed of Strychnou nux-vomica, and make comparison with the single components at the same concentration. METHOD: Ultrafiltration was employed to determine the rat the plasma protein binding rate of the alkaloids from the seed of S. nux-vomica. The plasma concentrations were measured by RP-HPLC. RESULT: The protein binding rates of brucine were (65.60 3.01)%, (68.20 +/- 7.80)%, (59.58 +/- 3.78)% when the plasma concentrations was 0.520, 1.300, 2.600 mg x L(-1), respectively. The protein binding rates of strychnine was (66.17 +/- 6.36)%, (67.10 +/- 2.52)%, (57.21 +/- 0.79)% when the plasma concentrations were 0.936, 2.340, 4.680 mg x L(-1) respectively. As to the total alkaloids from the seed of S. nux-vomica, The protein binding rate of brucine was (62.19 +/- 2.45)%, (69.55 +/- 5.84)%, (61.76 +/- 3.68)% when the plasma concentrations were 0.519, 1.288, 2.607 mg x L(-1), respectively. And the protein binding rates of strychnine were (54.79 +/- 3.55)%, (57.13 +/- 4.49)%, (59.31 +/- 3.65)% when the plasma concentrations were 0.940, 2.338, 4.674 mg x L(-1), respectively. CONCLUSION: Brucine and strychnine have medium capacity in binding to plasma protein. In comparison with the single component of the same concentration, the protein binding rate of brucine in total alkaloids shows little difference, while there seems to be an obvious decrease for strychnine.