Vertebral marrow fat fraction is associated with circulating RANKL in postmenopausal females.

Objective: To investigate the relationship between circulating receptor activator of nuclear factor-kappa B ligand (RANKL) levels and marrow adipose tissue in postmenopausal females. Methods: A total of 164 postmenopausal females were included in the study. Serum levels of osteoprotegerin (OPG) and RANKL were measured using ELISA kits. Body composition and bone mineral density (BMD) were assessed using dual-energy X-ray absorptiometry. Complex-based chemical shift imaging-based MRI was employed to evaluate the vertebral marrow proton density fat fraction (PDFF). A multivariate linear regression model was utilized to analyze the predictive effects of PDFF and BMD on circulating levels of OPG and RANKL. Results: Simple regression analysis showed significant associations among the marrow PDFF, BMD at either site, serum RANKL, and the RANKL/OPG ratio. In multivariate linear regression models, marrow PDFF was found to have a positive correlation (ß = 3.15, 95% CI 2.60 to 3.70) and BMD had negative correlations (ß = -0.200, 95% CI -0.348 to -0.051 for vertebral BMD; ß = -0.383, 95% CI -0.589 to -0.177 for total hip BMD; and ß =-0.393, 95% CI -0.598 to -0.188 for femoral neck BMD, all p < 0.01) with circulating soluble RANKL levels after adjusting for age, body mass index, physical activity, total fat mass, android/gynoid ratio, and lean mass. Similar results were observed for the RANKL/OPG ratio. Additionally, multivariate linear regression analyses revealed that marrow PDFF was a significant independent contributor of circulating soluble RANKL (ß = 1.34, 95% CI 1.10 to 1.58, p < 0.001) after further controlling for BMD. However, marrow PDFF or BMD had no associations with circulating levels of OPG after adjusting for all potential confounders mentioned above. Conclusions: Vertebral marrow fat fraction is independently associated with circulating soluble RANKL levels in postmenopausal females.

An Electrolyte Engineered Homonuclear Copper Complex as Homogeneous Catalyst for Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries suffer from severe polysulfide shuttle, retarded sulfur conversion kinetics and notorious lithium dendrites, which has curtailed the discharge capacity, cycling lifespan and safety. Engineered catalysts act as a feasible strategy to synchronously manipulate the evolution behaviors of sulfur and lithium species. Herein, a chlorine bridge-enabled binuclear copper complex (Cu-2-T) is in situ synthesized in electrolyte as homogeneous catalyst for rationalizing the Li-S redox reactions. The well-designed Cu-2-T provides completely active sites and sufficient contact for homogeneously guiding the Li2S nucleation/decomposition reactions, and stabilizing the lithium working interface according to the synchrotron radiation X-ray 3D nano-computed tomography, small angle neutron scattering and COMSOL results. Moreover, Cu-2-T with the content of 0.25 wt% approaching saturated concentration in electrolyte further boosts the homogeneous optimization function in really operated Li-S batteries. Accordingly, the capacity retention of the Li-S battery is elevated from 51.4% to 86.3% at 0.2 C, and reaches 77.0% at 1.0 C over 400 cycles. Furthermore, the sulfur cathode with the assistance of Cu-2-T realizes the stable cycling under the practical scenarios of soft-packaged pouch cell and high sulfur loading (6.5 mg cm-2 with the electrolyte usage of 4.5 µL mgS -1).

Gaining Insight into Updated MR Imaging for Quantitative Assessment of Cartilage Injury in Knee Osteoarthritis.

PURPOSE OF THE REVIEW: Knee Osteoarthritis (KOA) entails progressive cartilage degradation, reviewed via MRI for morphology, biochemical composition, and microtissue alterations, discussing clinical advantages, limitations, and research applicability. RECENT FINDINGS: Compositional MRI, like T2/T2* mapping, T1rho mapping, gagCEST, dGEMRIC, sodium imaging, diffusion-weighted imaging, and diffusion-tensor imaging, provide insights into cartilage injury in KOA. These methods quantitatively measure collagen, glycosaminoglycans, and water content, revealing important information about biochemical compositional and microstructural alterations. Innovative techniques like hybrid multi-dimensional MRI and diffusion-relaxation correlation spectrum imaging show potential in depicting initial cartilage changes at a sub-voxel level. Integration of automated image analysis tools addressed limitations in manual cartilage segmentation, ensuring robust and reproducible assessments of KOA cartilage. Compositional MRI techniques reveal microstructural changes in cartilage. Multi-dimensional MR imaging assesses biochemical alterations in KOA-afflicted cartilage, aiding early degeneration identification. Integrating artificial intelligence enhances cartilage analysis, optimal diagnostic accuracy for early KOA detection and monitoring.

Chlorine bridge bond-enabled binuclear copper complex for electrocatalyzing lithium-sulfur reactions.

Engineering atom-scale sites are crucial to the mitigation of polysulfide shuttle, promotion of sulfur redox, and regulation of lithium deposition in lithium-sulfur batteries. Herein, a homonuclear copper dual-atom catalyst with a proximal distance of 3.5 Å is developed for lithium-sulfur batteries, wherein two adjacent copper atoms are linked by a pair of symmetrical chlorine bridge bonds. Benefiting from the proximal copper atoms and their unique coordination, the copper dual-atom catalyst with the increased active interface concentration synchronously guide the evolutions of sulfur and lithium species. Such a delicate design breaks through the activity limitation of mononuclear metal center and represents a catalyst concept for lithium-sulfur battery realm. Therefore, a remarkable areal capacity of 7.8 mA h cm-2 is achieved under the scenario of sulfur content of 60 wt.%, mass loading of 7.7 mg cm-2 and electrolyte dosage of 4.8 µL mg-1.

Do Habitat MRI and Fractal Analysis Help Distinguish Triple-Negative Breast Cancer From Non-Triple-Negative Breast Carcinoma.

Purpose: To determine whether multiparametric MRI-based spatial habitats and fractal analysis can help distinguish triple-negative breast cancer (TNBC) from non-TNBC. Method: Multiparametric DWI and DCE-MRI at 3T were obtained from 142 biopsy- and surgery-proven breast cancer with 148 breast lesions (TNBC = 26 and non-TNBC = 122). The contrast-enhancing lesions were divided into 3 spatial habitats based on perfusion and diffusion patterns using K-means clustering. The fractal dimension (FD) of the tumour subregions was calculated. The accuracy of the habitat segmentation was measured using the Dice index. Inter- and intra-reader reliability were evaluated with the intraclass correlation coefficient (ICC). The ability to predict TNBC status was assessed using the receiver operating characteristic curve. Results: The Dice index for the whole tumour was 0.81 for inter-reader and 0.88 for intra-reader reliability. The inter- and intra-reader reliability were excellent for all 3 tumour habitats and fractal features (ICC > 0.9). TNBC had a lower hypervascular cellular habitat and higher FD 1 compared to non-TNBC (all P < .001). Multivariate analysis confirmed that hypervascular cellular habitat (OR = 0.88) and FD 1 (OR = 1.35) were independently associated with TNBC (all P < .001) after adjusting for rim enhancement, axillary lymph nodes status, and histological grade. The diagnostic model combining hypervascular cellular habitat and FD 1 showed excellent discriminatory ability for TNBC, with an AUC of 0.951 and an accuracy of 91.9%. Conclusions: The fraction of hypervascular cellular habitat and its FD may serve as useful imaging biomarkers for predicting TNBC status.

Deep white matter hyperintensity is spatially correlated to MRI-visible perivascular spaces in cerebral small vessel disease on 7 Tesla MRI.

BACKGROUND: The association between perivascular space (PVS) and white matter hyperintensity (WMH) has been unclear. Normal-appearing white matter (NAWM) around WMH is also found correlated with the development of focal WMH. This study aims to investigate the topological connections among PVS, deep WMH (dWMH) and NAWM around WMH using 7 Tesla (7T) MRI. METHODS: Thirty-two patients with non-confluent WMHs and 16 subjects without WMHs were recruited from our department and clinic. We compared the PVS burden between patients with and without WMHs using a 5-point scale. Then, the dilatation and the number of PVS within a radius of 1 cm around each dWMH were compared with those of a reference site (without WMH) in the contralateral hemisphere. In this study, we define NAWM as an area within the radius of 1 cm around each dWMH. Furthermore, we assessed the spatial relationship between dWMH and PVS. RESULTS: Higher PVS scores in the centrum semiovale were found in patients with >5 dWMHs (median 3) than subjects without dWMH (median 2, p = 0.014). We found there was a greater dilatation and a higher number of PVS in NAWM around dWMH than at the reference sites (p<0.001, p<0.001). In addition, 79.59% of the dWMHs were spatially connected with PVS. CONCLUSION: dWMH, NAWM surrounding WMH and MRI-visible PVS are spatially correlated in the early stage of cerebral small vessel disease. Future study of WMH and NAWM should not overlook MRI-visible PVS.

Dynorphin participates in interaction between depression and non-erosive reflux disease.

BACKGROUND: To explore the relationships between anxiety/depression and NERD, we focused on dynorphin (Dyn), an important member of visceral hypersensitivity, and its related pathways. METHODS: Pearson's correlation analysis on patients with NERD and in vivo experiment on NERD rat model. Part 1: Pearson's correlation analysis among serum levels of Dyn, clinical symptoms and HADS scores of NERD patients were carried on. Part 2: Wistar rats were randomly divided into 2 groups: control group and model group. The data of pH value, immobility time, serum Dyn concentration, NMDAR1 and SP expression were, respectively, derived from automatic pH recorder, tail suspension test, enzyme-linked immunosorbent assay, immunohistochemistry and immunofluorescence. RESULTS: Part 1: Pearson's correlation analysis showed that there was a linear correlation between Clinical Symptom (CS) score and HADS score (HAD-A, HAD-D), and the correlation coefficients were 0.385 and 0.273 respectively; the correlation coefficient between lg (Dyn) and lg (CS score) was r = 0.441, P = 0.002; the correlation coefficient between lg(Dyn) and lg (HAD-D score) was r = 0.447, P = 0.002. Part 2: The pH value of the lower esophagus in the model group was lower than that in the control group (P < 0.01). The tail suspension immobility time of model group was significantly longer than that of control group (P < 0.01). The serum Dyn concentration and the expression level of NMDAR1 in spinal cord and SP in lower esophageal mucosa of model group were significantly higher than those of control group (P < 0.05). CONCLUSION: Increased serum dynorphin level may be a sign of correlation between depression and NERD.

Comparison of Sensory Observation and Somatosensory Stimulation in Mirror Neurons and the Sensorimotor Network: A Task-Based fMRI Study.

Objective: This study aimed to investigate brain plasticity by somatosensory stimulation (SS) and sensory observation (SO) based on mirror neuron and embodied cognition theory. Action observation therapy has been widely adopted for motor function improvement in post-stroke patients. However, it is uncertain whether the SO approach can also contribute to the recovery of sensorimotor function after stroke. In this study, we explored the therapeutic potential of SO for sensorimotor dysfunction and provided new evidence for neurorehabilitation. Methods: Twenty-six healthy right-handed adults (12 men and 14 women), aged 18-27 (mean, 22.12; SD, 2.12) years were included. All subjects were evaluated with task-based functional magnetic resonance imaging (fMRI) to discover the characteristics and differences in brain activation between SO and SS. We adopted a block design with two conditions during fMRI scanning: observing a sensory video of brushing (task condition A, defined as SO) and brushing subjects' right forearms while they watched a nonsense string (task condition B, defined as SS). One-sample t-tests were performed to identify brain regions and voxels activated for each task condition. A paired-sample t-test and conjunction analysis were performed to explore the differences and similarities between SO and SS. Results: The task-based fMRI showed that the bilateral postcentral gyrus, left precentral gyrus, bilateral middle temporal gyrus, right supramarginal gyrus, and left supplementary motor area were significantly activated during SO or SS. In addition to these brain regions, SO could also activate areas containing mirror neurons, like the left inferior parietal gyrus. Conclusion: SO could activate mirror neurons and sensorimotor network-related brain regions in healthy subjects like SS. Therefore, SO may be a promising novel therapeutic approach for sensorimotor dysfunction recovery in post-stroke patients.

Effects of Total Flavonoids of Epimedium on Bone Marrow Adipose Tissue in Ovariectomized Rats.

Bone marrow adipose tissue has brown fat characteristics. Several studies have demonstrated that total flavonoids of Epimedium (TFE) could prevent bone loss and reduce the white adiposity in bone marrow induced by ovariectomy (OVX) in rats. However, the effects of TFE on marrow brown fat in OVX rats remain unclear. In this word, we addressed this question expected to provide a new target for preventing and treating osteoporosis. Thirty-six 3-month-old female Sprague-Dawley rats were equally divided into Sham controls, OVX controls, and OVX treated with TFE. Chemical shift coding magnetic resonance was performed to detect marrow fat fraction at the left femur at baseline, 6 and 12 weeks post-OVX. Bone mineral density at the lumbar spine and femur was measured by dual-energy x-ray absorptiometry. Serum bone biomarkers by ELISA, trabecular bone microarchitecture at the proximal tibia by micro-CT, quantitative parameters of marrow adipocyte by hematoxylin, and eosin staining were evaluated. The marrow adipocyte gene and protein expressions profile were determined by real-time quantitative PCR and immunostaining in whole tibiae. We found that TFE treatment could decrease bone turnover rate and improved bone mineral density and trabecular microarchitecture in OVX rats. OVX resulted in marrow adipogenesis as evidenced by increased marrow fat fraction, larger marrow adipocyte size, increased adipocyte number and percentage of adipocyte area, marrow white adipocyte gene, and protein expression, including PPARγ2 and FABP4. These pathological changes induced by estrogen deficiency were restored by TFE treatment. TFE also increased brown adipocyte expressions of the transcription factor Ucp1 and Prdm16 in whole tibiae. There was no detectible protein expression of brown adipocyte markers in the proximal tibia. Taken together, TFE regulation of bone marrow adiposity in OVX rats is mediated, at least in part, via maintaining the reciprocity of white and brown adipose tissue.

Association of Serum Ferritin With Marrow Iron Concentration Using a Three-Dimension Fat Analysis & Calculation Technique Sequence in Postmenopausal Women.

OBJECTIVE: The aim of the study was to determine whether serum iron and ferritin levels are determinants of iron accumulation in bone marrow using a three-dimension Fat Analysis & Calculation Technique (FACT) sequence. METHODS: We measured spinal marrow R2* using a 3T FACT sequence in 112 postmenopausal women (mean age, 62.6 years; range, 50-82.6 years). Serum iron and ferritin levels were determined in blood specimens. Lumbar spine bone mineral density was measured by dual-energy x-ray absorptiometry. The levels of serum iron and ferritin were evaluated in relation to the spinal marrow R2* values before and after adjustments for potential confounders. RESULTS: In the unadjusted model, magnetic resonance imaging-based spinal marrow R2* was positively correlated to the levels of serum ferritin (Spearman ρ = 0.436, P < 0.001) and iron (Spearman ρ = 0.245, P = 0.009). Multiple stepwise linear regression analyses (adjusting for age, years since menopause, body mass index, alcohol intake, tobacco use, physical activity, serum lipids profile, biomarkers of bone turnover, and lumbar spine bone density) were performed in 3 separate models with marrow R2* values as potential explanatory variables. The level of serum ferritin, but not iron, was an independent predictor of marrow R2* (standardized ß coefficient, 0.302, 95% confidence interval, 0.141-0.509, P = 0.001). Similarly, spinal marrow R2* increased with a linear trend from the lowest (<139 ng/mL) to highest (≥180 ng/mL) serum ferritin quartiles (P for trend = 0.007). CONCLUSIONS: Quantitative assessment of R2* derived from FACT is a fast, simple, noninvasive, and nonionizing method to evaluate marrow iron accumulation.

Tribo-electrochemistry induced artificial solid electrolyte interface by self-catalysis.

Potassium (K) metal is a promising alkali metal anode for its high abundance. However, dendrite on K anode is a serious problem which is even worse than Li. Artificial SEI (ASEI) is one of effective routes for suppressing dendrite. However, there are still some issues of the ASEI made by the traditional methods, e.g. weak adhesion, insufficient/uneven reaction, which deeply affects the ionic diffusion kinetics and the effect of inhibiting dendrites. Herein, through a unique self-catalysis tribo-electrochemistry reaction, a continuous and compact protective layer is successfully constructed on K metal anode in seconds. Such a continuous and compact protective layer can not only improve the K+ diffusion kinetics, but also strongly suppress K dendrite formation by its hard mechanical properties derived from rigid carbon system, as well as the improved K+ conductivity and lowered electronic conductivity from the amorphous KF. As a result, the potassium symmetric cells exhibit stable cycles last more than 1000 h, which is almost 500 times that of pristine K.

Correction: P62 regulates resveratrol-mediated Fas/Cav-1 complex formation and transition from autophagy to apoptosis.

[This corrects the article DOI: 10.18632/oncotarget.2733.].

Impact of Acupuncture on Sleep and Comorbid Symptoms for Chronic Insomnia: A Randomized Clinical Trial.

STUDY OBJECTIVES: To evaluate the efficacy and safety of acupuncture at HT 7 (Shenmen) and KI 7 (Fuliu) on sleep and comorbid symptoms for chronic insomnia. METHODS AND DESIGN: A randomized, single-blind, parallel and sham-controlled trial consisted of an acupuncture group (n = 41) and a sham acupuncture group (n = 41). Setting: a tertiary hospital of integrated Chinese and Western medicine. Participants: 82 subjects with chronic insomnia based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Interventions: a 10-session acupuncture treatment at bilateral HT 7 and KI 7 or sham acupoints with shallow needling was performed over 3 weeks. Measurements: the Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI) were evaluated at baseline, posttreatment, and at two follow-ups as the primary outcome measures. Polysomnography (PSG) on two consecutive nights, the Beck anxiety inventory (BAI), the Beck depression inventory (BDI) fatigue severity scale (FSS) and the Epworth sleepiness scale (ESS) were evaluated at baseline and posttreatment as the secondary outcome measures. RESULTS: After the treatments, PSQI scores decreased by 5.04 in the acupuncture group and 2.92 in the sham acupuncture group. ISI scores decreased by 7.65 in the acupuncture group and 5.05 in the sham acupuncture group. The between-group differences in the primary outcome measures posttreatment were statistically significant. However, no differences were found between the two groups during the two follow-ups. Regarding the PSG data, there were significantly lower levels of sleep onset latency (SOL), a lower percentage of sleep stage N1 and a higher percentage of sleep stage N3 in the acupuncture group than in the sham acupuncture group. After treatment, there were lower levels of comorbid symptoms (BAI, BDI, FSS and ESS) in both groups. However, no significant differences were observed between the groups. CONCLUSION: Acupuncture at HT 7 and KI 7 is an effective and safe nonpharmacologic intervention option for chronic insomnia. CLINICAL TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR1900023787, China.

Adding marrow R2∗ to proton density fat fraction improves the discrimination of osteopenia and osteoporosis in postmenopausal women assessed with 3D FACT sequence.

OBJECTIVE: To evaluate the role of three-dimensional Fat Analysis & Calculation Technique sequence in improving the diagnostic accuracy for the detection of osteopenia and osteoporosis by simultaneous quantification of proton density fat fraction (PDFF) and fat-corrected R2∗. METHODS: Fat Analysis & Calculation Technique imaging of lumbar spine was obtained in 99 postmenopausal women including 52 normal bone mass, 29 osteopenia, and 18 osteoporosis. The diagnostic performance of PDFF and R2∗ in the differentiation of different bone-density groups was evaluated with the receiver operating characteristic curve. RESULTS: The reproducibility of PDFF and R2∗ measures was satisfactory with the root mean square coefficient of variation, 2.16% and 2.70%, respectively. The intra- and interobserver agreements for the PDFF and R2∗ were excellent with the intraclass correlation coefficient > 0.9 for all. There were significant differences in PDFF and R2∗ among the three groups (P < 0.05). Bone density had a moderate inverse correlation with PDFF (r  = -0.659) but a positive association with R2∗ (r = 0.508, P < 0.001). Adjusted for age, years since menopause and body mass index, odds ratios (95% confidence interval) for osteopenia and osteoporosis per standard deviation higher marrow PDFF and R2∗ were 2.9 (1.4-5.8) and 0.4 (0.2-0.8), respectively. The areas under the curve were 0.821 for PDFF, 0.784 for R2∗, and 0.922 for both combined for the detection of osteoporosis (P < 0.05). Similar results were obtained in distinguishing osteopenia from healthy controls. CONCLUSIONS: Simultaneous estimation of marrow R2∗ and PDFF improves the discrimination of osteopenia and osteoporosis in comparison with the PDFF or R2∗ alone.

LC3B/p62-mediated mitophagy protects A549 cells from resveratrol-induced apoptosis.

AIMS: Complicated mechanisms in cancer cells have been restricting the medicinal value of resveratrol (Res). The mechanisms by which Res exerts its anti-tumor activity in lung cancer cells have diverged among reports in recent years, whether cells choose to undergo autophagic cell death or apoptosis remains controversial. Yet, whether Res-induced autophagic cell death transforms into apoptosis is still unknown, and by which autophagy regulates programmed cell death is still undefined. MAIN METHODS: Here, A549 cells were treated with Res to investigate the mechanisms of autophagy and apoptosis using western blot, immunofluorescence staining for LC3B. KEY FINDINGS: Non-canonical autophagy was induced by Res-treatment in a Beclin-1- and ATG5-independent manner, with apoptosis being activated simultaneously. Autophagy induced by Res was activated by rapamycin with decreased apoptosis, suggesting that autophagy may serve as a protective pathway in cells. Mitophagy was found to be induced by Res using fluorescence co-localization of mitochondria with lysosomes. Subsequently, it was identified that mitophagy was mediated by LC3B/p62 interaction and could be inhibited by LC3B knockout and p62 knockdown following increased apoptosis. SIGNIFICANCE: In conclusion, the current results demonstrate that Res-induced non-canonical autophagy in A549 lung cancer cells with apoptosis activation simultaneously, while LC3B/p62-mediated mitophagy protects tumor cells against apoptosis, providing novel mechanisms about the critical role of mitophagy in regulating cell fate.

Rapid remission of refractory synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome in response to the Janus kinase inhibitor tofacitinib: A case report.

BACKGROUND: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoinflammatory disease for which clinical treatment has not been standardized. Janus kinase (JAK) inhibitors represent a novel therapeutic option for rheumatoid arthritis, psoriatic arthritis, and some other autoinflammatory diseases. However, the clinical utility of JAK inhibitors in treating SAPHO syndrome has not been thoroughly investigated. In this study, we describe a patient with SAPHO syndrome who failed to respond to conventional treatment but demonstrated a remarkable and rapid response to the JAK inhibitor tofacitinib. CASE SUMMARY: A 62-year-old female patient presented with swelling and pain at the sternoclavicular joints, back pain that limited her activities, arthralgia in the right knee, and cutaneous lesions. Her symptoms were unresponsive to nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, Tripterygium wilfordii hook f, and bisphosphonates. SAPHO syndrome was diagnosed in accordance with dermatological and osteoarticular manifestations and abnormal inflammatory factors. Multiple image studies have illustrated bone lesions and pathological fractures of vertebral bodies. Oral treatment with tofacitinib at 5 mg twice daily with methotrexate and bisphosphonates was initiated. The patient reported that her pain symptoms were relieved after 3 d and her cutaneous lesions were reduced after 4 wk of treatment. Vertebral lesions were improved after 6 mo on tofacitinib. No serious adverse effects were noted. CONCLUSION: JAK inhibitor therapy may be a promising strategy to treat SAPHO syndrome.

Recombinant Human Growth Hormone Ameliorates Cognitive Impairment in Stroke Patients.

OBJECTIVE: We aimed to determine the effects of recombinant human growth hormone (rhGH) replacement on cognitive function in subjects with poststroke cognitive impairment using resting-state functional magnetic resonance imaging. METHODS: We included 60 patients with a first-ever stroke for 3 months and a diagnosis of cognitive impairment who were randomized 1:1 to receive either rhGH subcutaneously or placebo injection for 6 months. All subjects were required to receive the same rehabilitative therapy program. Both groups were subjected to pretreatment and posttreatment neuropsychological assessment using the Montreal Cognitive Assessment, serum neurotrophic factors, biomarkers of glucose and lipid metabolism, and functional magnetic resonance imaging during 6 months of the study period. The pattern of brain activity was determined by examining the functional connectivity and amplitude of low-frequency fluctuations (ALFF) of blood oxygen level dependent signal. RESULTS: Forty-three (82.7%) completed the study. Treatment with rhGH reduced levels of triglycerides and low-density lipoprotein cholesterol but did not significantly altered plasma concentrations of glucose and glycated hemoglobin. We found a significant increase in serum insulin-like growth factor 1 levels (32.6%; P < 0.001) in the rhGH-treated group compared with that in the controls. After 6 months of rhGH treatment, mean Montreal Cognitive Assessment score improved from 16.31 (5.32) to 21.19 (6.54) (P < 0.001). The rhGH group showed significant increased area of activation with increased ALFF values in the regions of the frontal lobe, putamen, temporal lobe, and thalamus (P < 0.05), relative to the baseline conditions. The correlation analysis revealed that the ALFF and functional connectivity of default mode network was positively correlated with the ΔMoCA score and ΔIGF-1 levels; that is, the more the scale score increased, the higher the functional connection strength. No undesirable adverse effects were observed. CONCLUSIONS: The rhGH replacement has a significant impact on global and domain cognitive functions in poststroke cognitive impairment.

Oncogenic functions of the EMT-related transcription factor ZEB1 in breast cancer.

Zinc finger E-box binding homeobox 1 (ZEB1, also termed TCF8 and δEF1) is a crucial member of the zinc finger-homeodomain transcription factor family, originally identified as a binding protein of the lens-specific δ1-crystalline enhancer and is a pivotal transcription factor in the epithelial-mesenchymal transition (EMT) process. ZEB1 also plays a vital role in embryonic development and cancer progression, including breast cancer progression. Increasing evidence suggests that ZEB1 stimulates tumor cells with mesenchymal traits and promotes multidrug resistance, proliferation, and metastasis, indicating the importance of ZEB1-induced EMT in cancer development. ZEB1 expression is regulated by multiple signaling pathways and components, including TGF-ß, ß-catenin, miRNA and other factors. Here, we summarize the recent discoveries of the functions and mechanisms of ZEB1 to understand the role of ZEB1 in EMT regulation in breast cancer.

Marrow adiposity as an indicator for insulin resistance in postmenopausal women with newly diagnosed type 2 diabetes - an investigation by chemical shift-encoded water-fat MRI.

BACKGROUND: Marrow fat accumulates in diabetic conditions but remains elusive. The published works on the relationships between marrow fat phenotypes and glucose homeostasis are controversial. PURPOSE: To detect the association of insulin resistance with marrow adiposity in postmenopausal women with newly diagnosed type 2 diabetes (T2D) using chemical shift-encoded water-fat MRI. METHODS: We measured vertebral proton density fat fraction (PDFF) by 3T-MRI in 75 newly diagnosed T2D and 20 nondiabetic postmenopausal women. Bone mineral density (BMD), whole body fat mass and lean mass were determined by dual-energy X-ray absorptiometry. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Lumbar spine PDFF was higher in women with T2D (65.9 ± 6.8%) than those without diabetes (59.5 ± 6.1%, P = 0.009). There was a consistent inverse association between the vertebral PDFF and BMD. PDFF had a positive association with glycated hemoglobin and HOMA-IR but not with fasting plasma glucose and insulin. PDFF was significantly increased, and BMD was decreased in a linear trend from the lowest (<1.90) to highest (≥2.77) HOMA-IR quartile. Multivariate linear regression analyses revealed a positive association between log-transformed HOMA-IR and PDFF after adjustment for multiple covariates (ß = 0.382, P < 0.001). The positive association of HOMA-IR with PDFF remained robust when total body lean mass and fat mass, BMD was entered into the multivariate regression model, respectively (ß = 0.293 and ß = 0.251, respectively; all P <0.05). CONCLUSIONS: Elevated HOMA-IR was linked to higher marrow fat fraction in postmenopausal women with newly diagnosed T2D independently of body compositions.

Effects of Shugan Hewei Granule on Depressive Behavior and Protein Expression Related to Visceral Sensitivity in a Rat Model of Nonerosive Reflux Disease.

OBJECTIVE: To explore the effect of Shugan Hewei Granule (SGHWG) and to provide the experimental basis for its clinical application. METHODS: 40 healthy male Wistar rats were divided into 5 groups, with 8 rats in each group, including control group, model group, normal saline (NS) group, SGHWG group, and Rabeprazole group. The control group was not treated. The model group was treated with fructose intake and mental stress to be the model of NERD. The other groups were treated as the model group and then gavaged with the corresponding drugs. The pH value of lower third of esophagus, immobile time in tail suspension test, CRF protein expression in both hypothalamus and anterior cingulate cortex (ACC), and SP protein in esophageal mucosa in lower third of esophagus detected by immunofluorescence and NMDAR1 protein expression in spinal cord detected by immunohistochemistry of each group were compared. RESULTS: The pH values of both the SGHWG group and the Rabeprazole group were higher than that of the model group (P<0.01), but the Rabeprazole group increased more obviously. The immobile time of the SGHWG group was shorter than that of the model group (P<0.01) and the Rabeprazole group (P<0.05). The expression of the CRF in the hypothalamus and ACC, NMDAR1 in the spinal cord, and SP in the esophageal mucosa in lower third of esophagus of the SGHWG group decreased significantly, compared with the model group (P<0.01), and was obviously lower than that in the Rabeprazole group (P<0.05). CONCLUSIONS: This study provided an evidence that SGHW formula was inferior to Rabeprazole in acid inhibition, but it might reduce the expression of CRF protein of hypothalamus and ACC, lower the levels of NMDAR1 in spinal dorsal horn and SP in esophageal mucosa in lower third of esophagus, and regulate depressive behavior simultaneously, related to the improvement of visceral hypersensitivity in rat model of NERD.