Risk factors of osteoporosis in elderly inpatients: A cross-sectional single-centre study.

Objective: This study aimed to identify factors significantly associated with the occurrence of osteoporosis in elderly and very elderly patients. Methods: Elderly hospitalized patients who were older than 60 years old, from the Rehabilitation Hospital from December 2019 to December 2020 were selected. Barthel index (BI), nutritional assessment, the causes of bone mineral density (BMD) reductions in elderly and elderly patients were analysed. Results: A total of 94 patients (83.56 ± 8.37 years old) were enrolled. With increasing age, the BMD of the lumbar spine, femoral neck, and femoral shaft of elderly patients significantly decreased, and the incidence of osteoporosis (OP) significantly increased. The BMD of the lumbar spine was negatively correlated with female and positively correlated with serum 25-hydroxyvitamin D levels, the difference between actual body weight and ideal body weight, and blood uric acid levels; The BMD of the femoral neck was negatively correlated with age and female, and positively correlated with height and geriatric nutrition risk index score. The BMD of the femoral shaft was negatively correlated with female and positively correlated with BI. Conclusion: With increasing age, the BMD of the lumbar spine and the femoral shaft significantly decreased, and the incidence of OP significantly increased in elderly and very elderly patients. Aric acid may protect bone health in elderly patients. Early attention to the nutritional status, exercise capacity, 25-hydroxyvitamin D level, and blood uric acid level in the elderly population can help identify high-risk elderly patients with OP.

Deep Image Steganography Using Transformer and Recursive Permutation.

Image steganography, which usually hides a small image (hidden image or secret image) in a large image (carrier) so that the crackers cannot feel the existence of the hidden image in the carrier, has become a hot topic in the community of image security. Recent deep-learning techniques have promoted image steganography to a new stage. To improve the performance of steganography, this paper proposes a novel scheme that uses the Transformer for feature extraction in steganography. In addition, an image encryption algorithm using recursive permutation is proposed to further enhance the security of secret images. We conduct extensive experiments to demonstrate the effectiveness of the proposed scheme. We reveal that the Transformer is superior to the compared state-of-the-art deep-learning models in feature extraction for steganography. In addition, the proposed image encryption algorithm has good attributes for image security, which further enhances the performance of the proposed scheme of steganography.

DNA methylation age acceleration is associated with age of onset in Chinese spinocerebellar ataxia type 3 patients.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado Joseph disease (MJD), is a common dominantly inherited ataxia, and has heterogeneous clinical features and variable age of onset, ranging from 10 to 78 years. Repeats variability of ATXN3, HTT, ATN1 and ATXN2 can explain partially but not fully SCA3 age of onset heterogeneity. Aging is a reported modifier of SCA3 severity and closely linked to DNA methylation (DNAm). DNAm age acceleration was associated with disease risk and/or variable disease phenotypes in several repeat associated neurodegenerative diseases (such as Huntington's disease and Amyotrophic lateral sclerosis). To understand if DNAm age acceleration is associated with SCA3 age of onset, we performed a genome-wide DNAm study of a Chinese SCA3 family with variable age of onset and clinical presentations. All patients showed unsteady gait, deterioration of extremities coordination, speech (dysarthria) and swallowing problems (dysphagia, choking on eating and/or drinking) and oculomotor abnormalities, with variable age of onset ranging from 27 to 52 years. We found that DNAm age acceleration is associated with age of onset (p-value = 0.0023, B = -1.26), suggesting that every 5 year increase in DNAm-age acceleration is corresponding to a 6.3 year earlier disease onset. This association remains significant after the adjustment to ATXN3 CAG repeats (adjusted p-value = 0.037, adjusted B = -1.0). In an independent SCA3 cohort (n = 40), we also observed the association between DNAm age acceleration and age of onset (adjusted p-value = 0.007, adjusted B = -0.69). Of note, we found no significant association between DNAm of single-CpG locus and/or CpG-SNPs and SCA3 age of onset in the current family or the SCA3 cohort. Our findings suggested that DNAm age acceleration might be a SCA3 age of onset modifier, and encourage further investigations in extended SCA3 cohorts to clarify the role of epigenetic aging in modifying disease onset.

Efficacy and safety of rivaroxaban and ticagrelor in elderly patients with atrial fibrillation undergoing percutaneous coronary intervention.

AIMS: To compare the efficacy and safety of a dual therapy (rivaroxaban and ticagrelor) with a triple therapy (aspirin, clopidogrel and warfarin) in Chinese elderly patients with nonvalvular atrial fibrillation (NVAF) undergoing percutaneous coronary intervention (PCI). METHODS: A total of 106 elderly Chinese patients with NAVF after PCI were randomly divided into a dual therapy group treated with ticagrelor 90 mg twice daily and rivaroxaban 15 mg once daily after PCI, and a triple therapy group treated with aspirin 100 mg and clopidogrel 75 mg once daily combined with the dose-adjusted vitamin K antagonist warfarin once daily. The mean follow-up time was 1 year. The primary endpoint was the composite death rate from cardiovascular causes, myocardial infarction, stroke or stent thrombosis. The safety endpoint was clinically significant bleeding (a composite value of major, minor and minimal bleeding). RESULTS: There were no significant differences between the 2 groups regarding the basic characteristics of the patients. The primary composite endpoint of the dual therapy group after 1 year was not significantly different from the triple therapy group (16.7% vs 15.2%, P = 0.86; HR 1.02; 95% CI: 0.82-1.24), but there was a significant difference in the incidence of hemorrhage (7.4% vs 26.9% P = 0.01; HR 0.71; 95% CI: 0.62-0.83) between the 2 groups. CONCLUSIONS: In elderly Chinese patients with NVAF undergoing PCI, the efficacy of dual (ticagrelor plus rivaroxaban) treatments was comparable to the triple antithrombotic regime (warfarin plus dual antiplatelet therapy). The overall incidence of bleeding was significantly reduced with dual treatment compared to the triple treatment regime.

MicroRNA-96 is required to prevent allodynia by repressing voltage-gated sodium channels in spinal cord.

Voltage-gated sodium channels (Navs) 1.7, 1.8, and 1.9 are predominately expressed in peripheral sensory neurons and are critical for action potential propagation in nociceptors. Unexpectedly, we found that expression of SCN9A, SCN10A, SCN11A, and SCN2A, the alpha subunit of Nav1.7, Nav1.8, Nav1.9 and Nav1.2, respectively, are up-regulated in spinal dorsal horn (SDH) neurons of miR-96 knockout mice. These mice also have de-repression of CACNA2D1/2 in DRG and display thermal and mechanical allodynia that could be attenuated by intrathecal or intraperitoneal injection of Nav1.7 or Nav1.8 blockers or Gabapentin. Moreover, Gad2::CreERT2 conditional miR-96 knockout mice phenocopied global knockout mice, implicating inhibitory neurons; nerve injury induced significant loss of miR-96 in SDH GABAergic and Glutamatergic neurons in mice which negatively correlated to up-regulation of Nav1.7, Nav1.8, Nav1.9 and Scn2a, this dis-regulation of miR-96 and Navs in SDH neurons contributed to neuropathic pain which can be alleviated by intrathecal injection of Nav1.7 or Nav1.8 blockers. In conclusion, miR-96 is required to avoid allodynia through limiting the expression of VGCCs and Navs in DRG and Navs in SDH in naïve and nerve injury-induced neuropathic pain mice. Our findings suggest that central nervous system penetrating Nav1.7 and Nav1.8 blockers may be efficacious for pain relief.

Exercise training attenuates cardiac inflammation and fibrosis in hypertensive ovariectomized rats.

This study investigated the effects of exercise training on cardiac inflammatory and cardiac fibrotic pathways in female spontaneously hypertensive rats (SHR), which were divided into a sham-operated sedentary hypertensive group (SHR-S), a sedentary hypertensive ovariectomized group (SHR-O), or a hypertensive ovariectomized group with treadmill exercise training (SHR-OT; 60 min/day, 5 days/wk) for 8 wk. Normotensive female Wistar-Kyoto rats (WKY) served as controls. SOD and catalase (CAT) activities were significantly increased in the SHR-OT group, when compared with the SHR-S or SHR-O groups. The protein levels of estrogen receptor (ER)-α and ER-ß became decreased in the SHR-O group, when compared with the WKY or SHR-S groups, but were not changed in the SHR-OT group. The protein level of the angiotensin II type I receptor (AT1R) was increased in the SHR-S group but did not further change in the SHR-O group, whereas it was decreased in the SHR-OT group. The inflammatory-related protein levels of TNF-α, p-NF-κB, cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), and IL-6, as well as the fibrotic-related protein levels of transforming growth factor-ß (TGF-ß), p-Smad2/3, connective tissue growth factor (CTGF), tissue-type plasminogen activator (tPA), matrix metalloproteinase (MMP)-9, and collagen I were increased in the SHR-S group and increased further in the SHR-O group, whereas they were decreased in the SHR-OT group. The coexistence of hypertension and ovariectomy additively increased cardiac inflammatory and fibrotic pathways partially through hypertension-enhanced AT1R and ovariectomy-depressed estrogen receptors. Exercise training appeared to suppress hypertensive ovariectomized heart-induced inflammatory and fibrotic pathways possibly through decreasing AT1R but not through estrogen receptors.NEW & NOTEWORTHY The coexistence of hypertension and ovariectomy appeared to increase cardiac inflammatory and fibrotic pathways likely through hypertension-enhanced angiotensin II type I receptor and ovariectomy-depressed estrogen receptors. Exercise training on a treadmill could prevent hypertensive ovariectomized heart-induced cardiac inflammation and fibrosis via an inflammatory pathway [TNF-α, p-IKK-α/ß, p-NF-κB, cyclooxygenase 2 (COX-2), iNOS, and IL-6] and fibrotic pathway [transforming growth factor-ß (TGF-ß), p-Smad2/3, connective tissue growth factor (CTGF), tissue-type plasminogen activator (tPA), matrix metalloproteinase (MMP)-9, and collagen I] possibly through decreasing angiotensin II type I receptor but not through estrogen receptors.

Lic regulates JNK-mediated cell death in Drosophila.

OBJECTIVES: The evolutionary conserved JNK pathway plays crucial role in cell death, yet factors that modulate this signalling have not been fully disclosed. In this study, we aim to identify additional factors that regulate JNK signalling in cell death, and characterize the underlying mechanisms. MATERIALS AND METHODS: Drosophila were raised on standard media, and cross was carried out at 25°C. The Gal4/UAS system was used to express proteins or RNAi in a specific temporal and spatial pattern. Gene expression was revealed by GFP fluorescence, X-gal staining or immunostaining of 3rd instar larval eye and wing discs. Cell death was visualized by acridine orange (AO) staining. Images of fly eyes and wings were taken by OLYMPUS microscopes. RESULTS: We found that licorne (lic) encoding the Drosophila MKK3 is an essential regulator of JNK-mediated cell death. Firstly, loss of lic suppressed ectopic Egr-triggered JNK activation and cell death in eye and wing development. Secondary, lic is necessary for loss-of-cell polarity-induced, physiological JNK-dependent cell death in wing development. Thirdly, Lic overexpression is sufficient to initiate JNK-mediated cell death in developing eyes and wings. Furthermore, ectopic Lic activates JNK signalling by promoting JNK phosphorylation. Finally, genetic epistatic analysis confirmed that Lic acts in parallel with Hep in the Egr-JNK pathway. CONCLUSIONS: This study not only identified Lic as a novel component of the JNK signalling, but also disclosed the crucial roles and mechanism of Lic in cell death.

MKK3 modulates JNK-dependent cell migration and invasion.

The c-Jun N-terminal kinase (JNK) pathway plays essential roles in regulating a variety of physiological processes including cell migration and invasion. To identify critical factors that regulate JNK-dependent cell migration, we carried out a genetic screen in Drosophila based on the loss-of-cell polarity-triggered cell migration in the wing epithelia, and identified MKK3 licorne (lic) as an essential regulator of JNK-mediated cell migration and invasion. We found that loss of lic suppressed ptc > scrib-IR or ptc > Egr triggered cell migration in the wing epithelia, and Rasv12/lgl-/- induced tumor invasion in the eye discs. In addition, ectopic expression of Lic is sufficient to induce JNK-mediated but p38-independent cell migration, and cooperate with oncogenic Ras to promote tumor invasion. Consistently, Lic is able to activate JNK signaling by phosphorylating JNK, which up-regulates the matrix metalloproteinase MMP1 and integrin, characteristics of epithelial-mesenchymal transition (EMT). Moreover, lic is required for physiological JNK-mediate cell migration in thorax development. Finally, expression of human MKK3 in Drosophila is able to initiate JNK-mediated cell migration, cooperates with oncogenic Ras to trigger tumor invasion, and rescue loss-of-lic induced thorax closure defect. As previous studies suggest that MKK3 specifically phosphorylates and activates p38MAPK, our data provide the first in vivo evidence that MKK3 regulates JNK-dependent cell migration and invasion, a process evolutionarily conserved from flies to human.

Diagnosis of chronic heart failure by the soluble suppression of tumorigenicity 2 and N-terminal pro-brain natriuretic peptide.

OBJECTIVE: Our study was to explore the roles between serum soluble suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) while evaluating ventricular function to properly diagnose chronic heart failure (CHF). METHODS: In total, 197 CHF patients were recruited and classified into ventricular function's II, III, and IV groups, and 106 healthy people into normal control group. To detect concentrations of Sst2 and NT-proBNP, ELISA and electro-chemiluminescence immuno assay were implemented. An automatic biochemical analyzer was used to determine the levels of the following: blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and uric acid (UA). A receiver operating characteristic (ROC) curve was adopted to detect the diagnostic value sST2 and NT-ProBNP in CHF and the logistic regression analysis involving the risk factors of CHF. RESULTS: Serum sST2 and NT-proBNP concentrations were increased significantly in the ventricular function's II, III, and IV groups in a manner dependent on concentration as opposed to the manner the normal control group occupied. The area under the curve (AUC) of sST2, found NT-proBNP and sST2+NT-proBNP to be 0.942 (95% CI: 0.917-0.966), 0.920 (95% CI: 0.891-0.948), and 0.968 (95% CI: 0.953-0.984), respectively. sST2, NT-proBNP, UA, and Cr were verified as important risk factors of CHF. CONCLUSION: Serum sST2 and NT-ProBNP could act as diagnostic indicators for CHF.

Cardiac structure and function improvements in coronary artery disease combined with severe obstructive sleep apnea/hypopnea syndrome patients via noninvasive positive pressure ventilation therapy.

OBJECTIVE: The aim of this study was to investigate the effects of a noninvasive positive pressure ventilation therapy on cardiac structure and function in patients with coronary heart disease combined with obstructive sleep apnea/hypopnea syndrome (OSAHS). PATIENTS AND METHODS: Eighty patients with coronary heart disease OSAHS were divided randomly into treatment (n=40) and control (n=40) groups. Both groups received standard medications. The treatment group received additional noninvasive mechanical ventilation support for at least 3 h (3-6 h) every night. On the first day after selection and 3 months afterwards, participants were examined with echocardiograms, 24-h ambulatory blood pressure monitoring, and blood analyses. Primary endpoints were left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, left atrial diameter as well as serum concentrations of N-terminal prohormone of brain natriuretic peptide, and high-sensitive C-reactive protein. Secondary endpoints included cardiac death, nonfatal myocardial infarction, and hospitalization. RESULTS: After the 3-month study period, patients in the treatment group showed significantly improved left ventricular end-diastolic diameter (P=0.02), left ventricular end-systolic diameter (P=0.035), left ventricular ejection fraction (P=0.05), and left atrial diameter (P=0.02) values, and their serum N-terminal prohormone of brain natriuretic peptide (P=0.01) and high-sensitive C-reactive protein (P=0.04) concentrations were significantly improved compared with the control group. During the 3 months, three cardiovascular complications occurred in the treatment group versus nine in the control group (P<0.05). CONCLUSION: For patients with coronary heart disease combined with OSAHS, noninvasive mechanical ventilation therapy can significantly improve heart functions and reduce the occurrence of cardiovascular complications.

Noninvasive positive pressure ventilation therapy can improve cardiac structure and function in patients with coronary artery disease combined with severe obstructive sleep apnea/hypopnea syndrome.

BACKGROUND: To investigate the effects of a noninvasive positive pressure ventilation therapy on cardiac structure and function in patients with coronary heart disease combined with obstructive sleep apnea/hypopnea syndrome (OSAHS). METHODS: 80 coronary heart disease OSAHS patients from three hospitals in Shanghai were randomly divided into treatment (n=40) and control (n=40) groups. Both groups received standard medications. The treatment group received an additional noninvasive mechanical ventilation support for at least 3 hours (3-6 hours) every night. On the first day after selection and 3 months afterwards participants were examined with echocardiograms, a 24-hour ambulatory blood pressure monitoring and blood analyses. Primary endpoints were left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVESd) and left ventricular ejection fraction (LVEF) as well as serum concentrations of N-terminal prohormone of brain natriuretic peptide (NT-ProBNP) and high sensitive C-reactive protein (hsCRP). Secondary endpoints included cardiac death, nonfatal myocardial infarction and hospitalization. RESULTS: After the 3 months study period, patients in the treatment group showed significant better improvements of LVEDd (p=0.02), LVESd (0.035) and LVEF (0.05) and their serum NT-ProBNP (p=0.01) and hsCRP (p=0.04) concentrations were significantly better improved than in the control group. During the 3 months, 3 cardiovascular complications occurred in the treatment group and 9 in the control group (p<0.05). CONCLUSIONS: For patients with coronary heart disease combined with obstructive sleep apnea/hypopnea syndrome, noninvasive mechanical ventilation therapy can significantly reduce left ventricular end systolic and end diastolic diameters, improve heart function and reduce the occurrence of cardiovascular complications.

Warfarin compared with aspirin for older Chinese patients with stable coronary heart diseases and atrial fibrillation complications.

OBJECTIVE: To compare the therapeutic warfarin and aspirin efficacies for treatments of atrial fibrillation (AF) complicated with stable coronary heart disease particularly in older Chinese patients. METHODS: In our prospective study 101 patients with AF and stable coronary heart disease older than 80 years were randomized into two groups. One group (n = 51) basically received 1.25 mg/day warfarin per os, followed by addition of 0.5 - 1.0 mg/day from day 3 - 5 if the international normalized ratio (INR) was initially < 1.5 and in order to achieve a maintained INR between 1.6 and 2.5 (warfarin group). The second group (n = 50) received 100 mg aspirin per day (control group). All patients were medicated and monitored for a period of 2 years. The primary endpoint was the occurrence of ischemic stroke or systemic embolism, and the composite secondary endpoint was non-fatal myocardial infarction and all causes of death. For safety evaluation, the hemorrhage rates were recorded. RESULTS: The warfarin medication was superior regarding the overall occurrence of ischemic stroke or systemic embolism as well as non-fatal myocardial infarction and all causes of death outcomes compared to aspirin administration during the 2 years of medication (17.6% vs. 36.0%, p = 0.03), while there was no significant difference of mild (5 vs. 4), severe (2 vs. 1), and fatal (1 vs. 1) hemorrhage incidences between the warfarin and aspirin groups (p > 0.05). CONCLUSION: Warfarin was found to be more efficacious than aspirin for an anticoagulation therapy of older Chinese patients with AF and stable coronary heart disease.