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.

Value of Hounsfield units measured by chest computed tomography for assessing bone density in the thoracolumbar segment of the thoracic spine.

STUDY DESIGN: A retrospective study. PURPOSE: To investigate the correlation between Hounsfield unit (HU) values measured by chest computed tomography (CT) and dual-energy Xray absorptiometry (DXA) T-scores. HU-based thoracolumbar (T11 and T12) cutoff thresholds were calculated for a cohort of Chinese patients. OVERVIEW OF LITERATURE: For patients with osteoporosis, the incidence of fractures in the thoracolumbar segment is significantly higher than that in other sites. However, most current clinical studies have focused on L1. METHODS: This retrospective study analyzed patients who underwent chest CT and DXA at our hospital between August 2021 and August 2022. Thoracic thoracolumbar segment HU values, lumbar T-scores, and hip T-scores were computed for comparison, and thoracic thoracolumbar segment HU thresholds suggestive of potential bone density abnormalities were established using receiver operating characteristic curves. RESULTS: In total, 470 patients (72.4% women; mean age, 65.5±12.3 years) were included in this study. DXA revealed that of the 470 patients, 90 (19%) had osteoporosis, 180 (38%) had reduced osteopenia, and 200 (43%) had normal bone mineral density (BMD). To differentiate osteoporosis from osteopenia, the HU threshold was established as 105.1 (sensitivity, 54.4%; specificity, 72.2%) for T11 and 85.7 (sensitivity, 69.4%; specificity, 61.1%) for T12. To differentiate between osteopenia and normal BMD, the HU threshold was 146.7 for T11 (sensitivity, 57.5%; specificity, 84.4%) and 135.7 for T12 (sensitivity, 59.5%; specificity, 80%). CONCLUSIONS: This study supports the significance of HU values from chest CT for BMD assessment. Chest CT provides a new method for clinical opportunistic screening of osteoporosis. When the T11 HU is >146.7 or the T12 HU is >135.7, additional osteoporosis testing is not needed unless a vertebral fracture is detected. If the T11 HU is <105.1 or the T12 HU is <85.7, further DXA testing is strongly advised. In addition, vertebral HU values that fall faster than those of the T11 and L1 vertebrae may explain the high incidence of T12 vertebral fractures.

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.

Microstructure Evolution and Mechanical Properties of Thick 2219 Aluminum Alloy Welded Joints by Electron-Beam Welding.

In this study, 2219 aluminum alloy thick plate was joined by electron beam welding. Defect-free joints with excellent surface formation were obtained. There were significant differences in the microstructure along the thickness direction of the weld zone (WZ). The upper region of the WZ was mainly striated grains, while the lower region was fine equiaxed grains. The WZ of 2219 joint is composed of α-Al and Al-Cu eutectic. Fine equiaxed grains were formed in the partially melted zone (PMZ) due to the existence of high-melting nucleation particles including Ti-Al and Ti-Zr compounds. The eutectic microstructure in the PMZ and the heat-affected zone (HAZ) presented net-like and block-shape distribution. Due to the formation of fine grains and high content of Al-Cu eutectic, the WZ showed the highest microhardness (80 HV). Therefore, the 2219 joint obtained excellent mechanical properties. The tensile strength of the 2219 joint was equal to that of the base metal (BM), but the elongation of the 2219 joint significantly decreased to 15.1%, about 67.7% of that of BM. The fracture mode of the 2219 joint presented typical ductile fracture.

Influence of Welding Speed on Microstructure and Mechanical Properties of 5251 Aluminum Alloy Joints Fabricated by Self-Reacting Friction Stir Welding.

In the present study, 8 mm-thick 5251 aluminum alloy was self-reacting friction stir welded (SRFSW) employing an optimized friction stir tool to analyze the effect of welding speed from 150 to 450 mm/min on the microstructure and mechanical properties at a constant rotation speed of 400 rpm. The results indicated that high-quality surface finish and defect-free joints were successfully obtained under suitable process parameters. The microhardness distribution profiles on the transverse section of joint exhibited a typical "W" pattern. The lowest hardness values located at the heat-affected zone (HAZ) and the width of the softened region decreased with increasing welding speed. The tensile strength significantly decreased due to the void defect, which showed mixed fracture characteristics induced by the decreasing welding speed. The average tensile strength and elongation achieved by the SRFSW process were 242.61 MPa and 8.3% with optimal welding conditions, and the fracture surface exhibited a typical toughness fracture mode.

Iridoids from Gardeniae fructus ameliorates depression by enhancing synaptic plasticity via AMPA receptor-mTOR signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Gardeniae fructus is a traditional Chinese herb which exerts antidepressant effect. However, its effective constituent and potential mechanism are still unknown. AIM OF THE STUDY: To examine whether iridoids, a type of monoterpenoids from Gardeniae fructus (IGF), exerts antidepressant effect by enhancing synaptic plasticity via AMPA receptor-mTOR signaling. MATERIALS AND METHODS: The antidepressant effect of IGF (15 mg/kg; 30 mg/kg; 45 mg/kg) was investigated in spatial restraint stress (SRS)-induced mice. The expression levels of AMPA receptor-mTOR signaling and synaptic proteins were measured by Western blot, dendritic spine density was observed in Golgi staining. AMPA receptor (AMPAR) inhibitor NBQX and mTOR inhibitor Rapamycin were employed to determine the roles of AMPAR and mTOR signaling in IGF-induced antidepressant effects. RESULTS: After IGF administration, the expression of the AMPA glutamate receptor Glutamate Receptor 1 (GluA1) was inhibited in SRS mice. We also observed a trend toward the up-regulation of the mammalian target of Rapamycin (mTOR) protein kinase, p70 ribosomal protein S6K (P70S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1). The protein levels of Synapsin-1 and PSD-95 were decreased after SRS challenge, along with declined dendritic spine density, which were all reversed with IGF treatment. Furthermore, the treatment efficacy of IGF were blocked with AMPA receptor inhibitor NBQX or mTOR inhibitor Rapamycin. CONCLUSION: IGF exerted antidepressive-like effects by stimulating AMPAR-mTOR signaling regulated synaptic plasticity enhancement. This work provided an important basis for developing IGF and Gardeniae fructus as potential anti-depressants.

Combinatory transplantation of mesenchymal stem cells with flavonoid small molecule in acellular nerve graft promotes sciatic nerve regeneration.

Previous animal studies have demonstrated that the flavonoid small-molecule TrkB agonist, 7, 8-dihydroxyflavone (DHF), promotes axon regeneration in transected peripheral nerves. In the present study, we investigated the combined effects of 7, 8-DHF treatment and bone marrow-derived stem/stromal cells (BMSCs) engraftment into acellular nerve allografts (ANAs) and explore relevant mechanisms that may be involved. Our results show that TrkB and downstream ERK1/2 phosphorylation are increased upon 7, 8-DHF treatment compared to the negative control group. Also, 7, 8-DHF promotes proliferation, survival, and Schwann-like cell differentiation of BMSCs in vitro. While selective ERK1/2 inhibitor U0126 suppressed the effect of upregulation of ERK1/2 phosphorylation and decreased cell proliferation, survival, and Schwann-like cell differentiation partially induced by 7, 8-DHF. In vivo, 7, 8-DHF promotes survival of transplanted BMSCs and upregulates axonal growth and myelination in regenerating ANAs. 7, 8-DHF+BMSCs also improved motor endplate density of target musculature. These benefits were associated with increased motor functional recovery. 7, 8-DHF+BMSCs significantly upregulated TrkB and ERK1/2 phosphorylation expression in regenerating ANA, and increased TrkB expression in the lumbar spinal cord. The mechanism of 7, 8-DHF action may be related to its ability to upregulate TrkB signaling, and downstream activation of survival signaling molecules ERK1/2 in the regenerating ANAs and spinal cord and improved survival of transplanted BMSCs. This study provides novel foundational data connecting the benefits of 7, 8-DHF treatment in neural injury and repair to BMSCs biology and function and demonstrates a potential combination approach for the treatment of injured peripheral nerve via nerve graft transplant.

The antidepressant effects of apigenin are associated with the promotion of autophagy via the mTOR/AMPK/ULK1 pathway.

The present study aimed to investigate whether apigenin elicits antidepressant effects in depressant­like mice via the regulation of autophagy. The depressant­like behaviors were established in a chronic restraint stress model. Male BALB/c mice were subjected to restraint stress for 6 h/day for a period of 21 days, and deficits in sucrose preference, tail suspension and forced swim tests were confirmed to be improved following oral apigenin. To investigate the underlining mechanisms, the hippocampal levels of p62 and microtubule­associated protein light chain 3­II/I (LC3­II/I) were measured using western blot analysis. The expression levels of LC3­II/I and p62 indicated that the significantly inhibited autophagy level induced by chronic restraint stress can be increased following apigenin treatment. Similar to the level of autophagy, the expression levels of adenosine monophosphate­activated protein kinase (AMPK) and Unc­51 like autophagy activating kinase­1 were downregulated after chronic restraint stress stimulation and, subsequently upregulated following treatment with apigenin. Conversely, the levels of mammalian target of rapamycin (mTOR) were increased in chronic restraint stress mice and inhibited by apigenin. Collectively, the present findings indicated that apigenin potentially promotes autophagy via the AMPK/mTOR pathway and induces antidepressive effects in chronic restraint stress mice.

KLF7 overexpression in bone marrow stromal stem cells graft transplantation promotes sciatic nerve regeneration.

OBJECTIVE: Our previous study demonstrated that the transcription factor, Krüppel-like Factor 7 (KLF7), stimulates axon regeneration following peripheral nerve injury. In the present study, we used a gene therapy approach to overexpress KLF7 in bone marrow-derived stem/stromal cells (BMSCs) as support cells, combined with acellular nerve allografts (ANAs) and determined the potential therapeutic efficacy of a KLF7-transfected BMSC nerve graft transplantation in a rodent model for sciatic nerve injury and repair. APPROACH: We efficiently transfected BMSCs with adeno-associated virus (AAV)-KLF7, which were then seeded in ANAs for bridging sciatic nerve defects. MAIN RESULTS: KLF7 overexpression promotes proliferation, survival, and Schwann-like cell differentiation of BMSCs in vitro. In vivo, KLF7 overexpression promotes transplanted BMSCs survival and myelinated fiber regeneration in regenerating ANAs; however, KLF7 did not improve Schwann-like cell differentiation of BMSCs within in the nerve grafts. KLF7-BMSCs significantly upregulated expression and secretion of neurotrophic factors by BMSCs, including nerve growth factor, ciliary neurotrophic factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in regenerating ANA. KLF7-BMSCs also improved motor axon regeneration, and subsequent neuromuscular innervation and prevention of muscle atrophy. These benefits were associated with increased motor functional recovery of regenerating ANAs. SIGNIFICANCE: Our findings suggest that KLF7-BMSCs promoted peripheral nerve axon regeneration and myelination, and ultimately, motor functional recovery. The mechanism of KLF7 action may be related to its ability to enhance transplanted BMSCs survival and secrete neurotrophic factors rather than Schwann-like cell differentiation. This study provides novel foundational data connecting the benefits of KLF7 in neural injury and repair to BMSC biology and function, and demonstrates a potential combination approach for the treatment of injured peripheral nerve via nerve graft transplant.

Crocin induces anti-ischemia in middle cerebral artery occlusion rats and inhibits autophagy by regulating the mammalian target of rapamycin.

Crocin, an active compound found in Gardenia jasminoides Ellis, has been shown to possess neuron-protective properties, but its potential mechanisms of action still remain poorly understood. In this study, the anti-ischemic effect and underlying mechanism of action of crocin were investigated in male rats with right middle cerebral artery occlusion/reperfusion. Computed tomography and magnetic resonance imaging were used to evaluate the area of infarction 24 h after reperfusion. Neurological scores were employed to evaluate nerve injury. Direct 2,3,5-triphenyltetrazolium chloride staining was used to calculate the infarct ratio 120 h after reperfusion. Finally, HT22 cells and Western blot were used to study the underlying mechanisms. Crocin showed a decreased infarct volume and neurological score in vivo, while the expression of LC3-II/I and AMP-activated protein kinase was remarkably down-regulated with increased levels of p62 and mammalian target of rapamycin (mTOR) expression. However, rapamycin significantly inhibited mTOR, which can impact the anti-ischemic effect of crocin in vitro. These results suggest that crocin may elicit an anti-ischemic effect probably through the mTOR pathway.

The antidepressant effects of ɑ-tocopherol are related to activation of autophagy via the AMPK/mTOR pathway.

The purpose of the present study was to investigate whether ɑ-tocopherol exhibited neuro-protective effects in chronic unpredictable mild stress (CUMS) mice through the regulation of autophagy. Deficits in behavioural tests, including a sucrose preference test, open field test, forced swim test, and tail suspension test, were ameliorated following ɑ-tocopherol administration. To study the potential mechanism, western blots were performed on both prefrontal cortex and hippocampus samples. Similar to the degree of autophagy, the activities of adenosine monophosphate-activated protein kinase (AMPK) and Unci-51 like autophagy activating kinase-1 (ULK1) were decreased after CUMS stimulation. In addition, we also found increased activity of the mammalian target of rapamycin (mTOR), which was significantly affected following administration of ɑ-tocopherol, as well as its three downstream pathways. Taken together, our study found that ɑ-tocopherol might potentially promote autophagy to induce anti-depressive responses in CUMS mice though the AMPK/mTOR pathway.

Extract of Euryale ferox Salisb exerts antidepressant effects and regulates autophagy through the adenosine monophosphate-activated protein kinase-UNC-51-like kinase 1 pathway.

Positive regulation of autophagy by Euryale ferox Salisb (ES) leads to antidepressant effects. This study focused on the potential antidepressant mechanisms induced by the petroleum ether fraction of ES (ES-PE) in the chronically unpredictable mild stress (CUMS) mouse model. Deficits in the sucrose preference test, open field test, tail suspension test, and forced swim test were observed following CUMS, and were reversed following ES-PE administration. Contrary to the expression of mammalian target of rapamycin, autophagy was decreased after establishment of the CUMS model. We also observed trends for downregulation of adenosine mononphosphate-activated protein kinase (AMPK) and mammalian autophagy-initiating kinase (ULK1), which were differentially affected by ES-PE. HT22 cells and Compound C, an inhibitor of AMPK, were used to verify the results in mice. Gas chromatography-mass spectrometry analysis revealed high level of vitamin E acetate in ES-PE. Taken together, our data indicate that ES-PE activated autophagy by regulating the AMPK pathway. © 2018 IUBMB Life, 70(4):300-309, 2018.

[Simultaneous determination of 87 pesticides in river water and seawater using solid phase extraction-gas chromatography-mass spectrometry].

A method for the simultaneous determination of 87 commonly used pesticides in China including 24 organophosphorous pesticides, 15 organochlorine pesticides, 12 azoles, 9 pyrethroids, 7 amides and anilines, 5 carbamates and other 15 pesticides in river water and seawater was established using solid phase extraction (SPE)-gas chromatography-mass spectrometry (GC-MS). GC-MS parameters influencing separation and sensitivity were optimized, and the effects of sample volume, pH and salinity on SPE were investigated. The purification was performed using NH2 SPE cartridge. An internal standard and 5 surrogates were used for data analysis and quality control. The results indicated that under the optimized conditions the limits of detection were in the range of 0.1 - 6.6 ng/L. For most target pesticides, recoveries were between 60% and 120% with relative standard deviations (RSDs, n = 4) of 0.01% - 9.7% at the spiked levels of 5 ng/L and 20 ng/L in real river water and sea water matrices. The method was successfully applied to monitor multi-class pesticides in surface water in Fujian Jiulong estuary, and 20 pesticides including 5 organophosphorous pesticides, 3 amides, 4 azoles, 3 carbamates, 2 pyrethroids and 3 other pesticides were detected in the mass concentration range of 1.18 - 660.93 ng/L. The proposed method can meet the requirement for the determination of trace pesticide residues in water samples.

Antibiotics pollution in Jiulong River estuary: source, distribution and bacterial resistance.

To gain insight into the antibiotic pollution in the Jiulong River estuary and the pollutant sources, we analyzed the concentration of 22 widely-used antibiotics in water samples collected from the river and estuary, 17 and 18 sampling sites, respectively. Contamination with sulfonamides, quinolones and chloramphenicols was frequently detected and the distribution pattern of antibiotics suggested that most of the pollutants are from the Jiulong River, especially from the downstream watersheds. To reveal the ecological effects, we isolated 35 bacterial strains from the estuary and analyzed their antibiotic resistance to the eight most frequently detected antibiotics. The bacteria were subsequently classified into seven different genera by 16SrDNA sequencing. Up to 97.1% of the bacteria showed resistance and 70.6% of strains showed multi-resistance to these antibiotics, especially to sulfonamides. This study demonstrated a pattern of antibiotic contamination in the Jiulong River and its estuary and illustrated high bacterial antibiotic resistance which was significantly correlated with the average antibiotics concentrations and detected frequencies in the estuary.

[Simultaneous determination of tetracycline and quinolone antibiotics in environmental water samples using solid phase extraction-ultra pressure liquid chromatography coupled with tandem mass spectrometry].

Using HLB cartridge for extraction and cleanup, a method for simultaneous determination of 4 tetracycline and 6 quinolone antibiotics in environmental water samples was developed by ultra pressure liquid chromatography coupled with tandem mass spectrometry. Using river water and sea water as matrices and carbadox as surrogate, the recoveries and relative standard deviations (RSD, n = 4) were 94.0% - 117.0% and 2.0% - 9.7% for 4 tetracyclines at 20.0 ng/L and 100.0 ng/L spiking levels and 63.6% - 93.9% and 1.6% - 8.1% for 6 quinolones at 5.0 ng/L and 20.0 ng/L spiking levels, respectively. The detection limits were 20.0 ng/L for 4 tetracyclines and 0.4 ng/L for 6 quinolones. The method has been successfully applied to the survey of 10 target antibiotic residues in Jiulong River estuary, Fujian.

[Determination of nine triazole pesticides in environmental waters using solid phase extraction and gas chromatography-mass spectrometry].

A method was developed for the simultaneous determination of 9 triazole pesticides in environmental water using C18 cartridge for the extraction and enrichment, NH2 cartridge for the clean-up and gas chromatography-mass spectrometry for the detection. The linear range of calibration curves for the 9 target pesticides was between 0.025 mg/L and 0.500 mg/L. The detection limits were in the range of 0.002 - 0.009 microg/L. The 9 target pesticides were measured in river water and sea water at 0.025 microg/L and 0.100 microg/L spiking levels, recoveries and relative standard deviations (RSD, n = 3) were 68.4% - 113.9% and 1.6% - 6.9% for river water and 70.3% - 115.2% and 0.8% - 8.2% for sea water, respectively. The method is simple, sensitive, selective and suitable for the qualification of pesticide multiresidue analysis. It has been successfully applied to the survey of 9 triazole pesticide residues in Jiulong River Estuary, Fujian.