Treatment algorithms of relapsing multiple sclerosis: an exploration based on the available disease-modifying therapies in China.

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon ß was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country.

Treatment algorithms of relapsing multiple sclerosis in China In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country: 1) CIS and RRMS account for more than 90% of the MS patients and most of them are mild to moderate; 2) MS patients should initiate DMT treatments as soon as the disease has been diagnosed in order to reduce the risk of disease progression; 3) Patients who have been diagnosed with MS should start treatment with fundamental DMTs unless the disease course has been highly active; 4) MAGNIMS score may be a suitable and simplified assessment tool for measuring treatment response to DMTs; 5) Patients treated with corticosteroids and NSIS should be switched to the standardized DMT treatment during remission in accordance with disease activity.

Trajectories of depressive symptom and its association with air pollution: evidence from the Mr. OS and Ms. OS Hong Kong cohort study.

BACKGROUND: Depression is a global health priority. Maintaining and delaying depressive symptoms in older adults is a key to healthy aging. This study aimed to identify depressive symptom trajectories, predictors and mortality, while also exploring the relationship between air quality and depressive symptoms in older adults in the Hong Kong community over 14 years. METHODS: This study is a longitudinal study in Hong Kong. The target population was community-dwelling older adults over age 65. Depressive symptoms were measured by the Geriatric Depression Scale (GDS-15). Group-based trajectory model was used to identify heterogeneity in longitudinal changes over 14 years and examine the associations between baseline variables and trajectories for different cohort members using multinomial logistic regression. The Kaplan-Meier method was employed to conduct survival analysis and explore the variations in survival probabilities over time among different trajectory group. Linear mixed model was used to explore the relationship between air quality and depressive symptoms. RESULTS: A total of 2828 older adults were included. Three different trajectories of depressive symptoms in older people were identified: relatively stable (15.4%), late increase (67.1%) and increase (17.5%). Female, more number of chronic diseases, poor cognitive function, and poor health-related quality of life (HRQOL) were significantly associated with other less favorable trajectories compared with participants with stable levels of depressive symptoms. The late increase group had a lower mortality rate than the relatively stable and increased groups. Lower baseline ambient air pollutant exposure to NO2 over 14 years was significantly associated with fewer depressive symptoms. CONCLUSIONS: In this study, we found that a late increase in depressive symptoms was the predominant trend in older Chinese people in Hong Kong. Poorer HRQOL was predictive of less favorable trajectories of depressive symptoms. Ambient air pollution was associated with depressive symptoms. This novel observation strengthens the epidemiological evidence of longitudinal changes in depressive symptoms and associations with late-life exposure to air pollution.

Evaluation of the Correlation Between Distribution Location and Vulnerability of Carotid Plaque in Patients with Transient Ischemic Attack.

Purpose: To analyze the relationship among distribution location, characteristics, and vulnerability of carotid plaque using CTA and provide more information on the risk factors of carotid atherosclerotic plaque. Patients and Methods: We retrospectively analyzed the CTA images of the head and neck of 93 patients with carotid atherosclerosis. Atherosclerosis was developed in 148 carotid arteries. The plaques were divided into a high-risk plaque group and a low-risk plaque group according to whether the plaques had high-risk characteristics. The maximum cross-sectional area of carotid artery bifurcation plaque on the axial image was selected, and the cross-sectional lumen was equally divided into four 90-degree sectors, ventral side wall, dorsal side wall, inner side wall, and outer side wall. The differences in the characteristics and distribution locations of the plaques in the two groups were analyzed. The characteristic parameters of the cross-sectional plaques at the bifurcation of the carotid artery. The logistic regression analysis was used to further analyze the risk factors associated with plaque vulnerability. Results: Among 148 carotid arteries,80 were classified as high-risk and 68 as low-risk groups. There were significant differences between the two groups concerning the thickness, length, maximum cross-sectional area, burden, and cross-sectional distribution of the plaques (P < 0.05). The plaque distribution on the dorsal side wall of the carotid bifurcation was higher in the high-risk group than that in the low-risk group (P < 0.05), dorsal side wall plaque-independent risk factors for the development of vulnerability of plaques in transient ischemic attack (TIA) patients (95% CI:1.522~6.991, P<0.05). Conclusion: High-risk plaques tend to occur on the dorsal side wall of the carotid bifurcation, whereas low-risk plaques tend to occur on the outer side wall of the carotid bifurcation.

Sucrose ester embedded lipid carrier for DNA delivery.

Sucrose esters (SEs) have great potential in the field of nucleic acid delivery due to their unique physical and chemical properties and good biosafety. However, the mechanism of the effect of SEs structure on delivery efficiency has not been studied. The liposomes containing peptide lipids and SEs were constructed, and the effects of SEs on the interaction between the liposomes and DNA were studied. The addition of SEs affects the binding rate of liposomes to DNA, and the binding rate gradually decreases with the increase of SEs' carbon chain length. SEs also affect the binding site and affinity of liposomes to DNA, promoting the aggregation of lipids to form liposomes, where DNA wraps around or compresses inside the liposomes, allowing it to compress DNA without damaging the DNA structure. COL-6, which is composed of sucrose laurate, exhibits the optimal affinity for DNA, and SE promotes the formation of ordered membrane structure and enhances membrane stability, so that COL-6 exhibits a balance between rigidity and flexibility, and thus exhibits the highest delivery efficiency of DNA among these formulations. This work provides theoretical foundations for the application of SE in gene delivery and guides for the rational design of delivery systems.

Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG. METHODS: By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk. RESULTS: We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk. CONCLUSIONS: This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.

The Inhibition Mechanisms of Three Structurally Different Salvianolic Acids on the Non-Enzymatic Glycation of Bovine Serum Albumin.

The antiglycation mechanisms of three structurally different salvianolic acids (Sals) including salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and salvianolic acid C (Sal-C) were investigated using the bovine serum albumin (BSA)-fructose model. The results showed that the three compounds could inhibit the formation of glycation products, maintain protein structural stability, mitigate the development of amyloid fibrils and scavenge radicals. Notably, Sal-A possessed the highest anti-glycated activity compared with Sal-B and Sal-C. This may be related to the fact that Sal-A contained the most molecules of caffeic acid (Sal-A, Sal-B, and Sal-C possessing two, one, and zero caffeic acid units, respectively), and caffeic acid played a leading role in the antiglycation properties relative to Danshensu. Moreover, these compounds quenched the intrinsic fluorescence intensity of BSA in a static mode, with the binding constants in the order of Sal-A > Sal-B > Sal-C. Obviously, Sal-A possessed the strongest binding affinity among these compounds, which may be one of the reasons why it exhibited the optimal antiglycation capability. Furthermore, molecular docking demonstrated that the three Sals exerted protective effects on BSA by preventing glycation modification of lysine and arginine residues. These findings would provide valuable insights into the potential application of Sals for alleviating non-enzymatic glycation of protein.

Maternal Ezh1/2 deficiency impairs the function of mitochondria in mouse oocytes and early embryos.

Maternal histone methyltransferase is critical for epigenetic regulation and development of mammalian embryos by regulating histone and DNA modifications. Here, we reported a novel mechanism by revealing the critical effects of maternal Ezh1/2 deletion on mitochondria in MII oocytes and early embryos in mice. We found that Ezh1/2 knockout in mouse MII oocytes impaired the structure of mitochondria and decreased its number, but membrane potential and respiratory function of mitochondrion were increased. The similar effects of Ezh1/2 deletion have been observed in 2-cell and morula embryos, indicating that the effects of maternal Ezh1/2 deficiency on mitochondrion extend to early embryos. However, the loss of maternal Ezh1/2 resulted in a severe defect of morula: the number, membrane potential, respiratory function, and ATP production of mitochondrion dropped significantly. Content of reactive oxygen species was raised in both MII oocytes and early embryos, suggesting maternal Ezh1/2 knockout induced oxidative stress. In addition, maternal Ezh1/2 ablation interfered the autophagy in morula and blastocyst embryos. Finally, maternal Ezh1/2 deletion led to cell apoptosis in blastocyst embryos in mice. By analyzing the gene expression profile, we revealed that maternal Ezh1/2 knockout affected the expression of mitochondrial related genes in MII oocytes and early embryos. The chromatin immunoprecipitation-polymerase chain reaction assay demonstrated that Ezh1/2 directly regulated the expression of genes Fxyd6, Adpgk, Aurkb, Zfp521, Ehd3, Sgms2, Pygl, Slc1a1, and Chst12 by H3K27me3 modification. In conclusion, our study revealed the critical effect of maternal Ezh1/2 on the structure and function of mitochondria in oocytes and early embryos, and suggested a novel mechanism underlying maternal epigenetic regulation on early embryonic development through the modulation of mitochondrial status.

An arabinose-rich heteropolysaccharide isolated from Belamcanda chinensis (L.) DC treats liver cancer by targeting FAK and activating CD40.

An undisclosed polysaccharide, BCP80-2, was isolated from Belamcanda chinensis (L.) DC. Structural investigation revealed that BCP80-2 consists of ten monosaccharide residues including t-α-Araf-(1→, →3,5)-α-Araf-(1→, →5)-α-Araf-(1→, →4)-ß-Xylp-(1→, →3)-α-Rhap-(1→, →4)-ß-Manp-(1→, t-ß-Glcp-(1→, →6)-α-Glcp-(1→, t-ß-Galp-(1→, and→3)-α-Galp-(1→. In vivo activity assays showed that BCP80-2 significantly suppressed neoplasmic growth, metastasis, and angiogenesis in zebrafish. Mechanistic studies have shown that BCP80-2 inhibited cell migration of HepG2 cells by suppressing the FAK signaling pathway. Moreover, BCP80-2 also activated immunomodulation and upregulated the secretion of co-stimulatory molecules CD40, CD86, CD80, and MHC-II. In conclusion, BCP80-2 inhibited tumor progression by targeting the FAK signaling pathway and activating CD40-induced adaptive immunity.

Intrinsic capacity trajectories, predictors and associations with care dependence in community-dwelling older adults: A social determinant of health perspective.

AIMS: To identify intrinsic capacity trajectories, predictors of intrinsic capacity trajectories and associations between intrinsic capacity trajectories and care dependence in community-dwelling older adults in China. METHODS: A retrospective longitudinal study was conducted, and the data were obtained from a five-year national longitudinal cohort study of older adults in China between 2011 and 2015. The social determinants of health framework informed the data analysis and interpretation. RESULTS: A total of 3893 older adults met the selection criteria and were included in the study. Three intrinsic capacity trajectories were identified: high trajectory (15.7 %), stable trajectory (52.7 %) and declining trajectory (31.6 %). Social determinants contribute to intrinsic capacity decline in older adults. Decreased cognitive function, psychological status, and locomotion at baseline were associated with care dependence. CONCLUSION: Approximately thirty percent of the older adults in this cohort study experienced a decline in intrinsic capacity within a 5-year period. Social determinants contributed to this decline in older adults.

A novel predictive model based on pericarotid adipose tissue and lumen stenosis for stroke risk in patients with asymptomatic carotid stenosis.

The study aimed to investigate the predictive value of clinical characteristics, major computed tomography angiography (CTA) indexes of carotid AS (carotid lumen stenosis and plaque burden), and inflammatory pericarotid adipose tissue for acute stroke risk in patients with a moderate or higher degree of carotid stenosis. In all, 119 patients with unilateral carotid stenosis who underwent head and neck computed tomography angiography were included and assigned to the stroke group or non-stroke group according to magnetic resonance imaging. Pericarotid adipose tissue attenuation value, net enhancement value in the base phase and the enhancement phase, and atherosclerotic features (plaque burden and lumen stenosis) were recorded. Multivariate logistic regression analysis and the operating characteristic curve (ROC) were performed to establish a predictive model for the presence of acute ischemic stroke. ROC analysis showed that pericarotid adipose tissue attenuation value and lumen stenosis were predictive factors for stroke. The AUC of pericarotid adipose tissue attenuation (PCAT) attenuation, lumen stenosis, the novel prediction model independently constructed based on PCAT attenuation, and lumen stenosis resulted in 0.838 (95% CI 0.759-0.899), 0.700 (95% CI 0.826-0.944), and 0.942 (95% CI 0.884-0.977), respectively. The model had a sensitivity and specificity of 0.909 and 0.893, respectively, when the cutoff value was 0.388. We found that the risk model combining pericarotid adipose tissue attenuation value and lumen stenosis has significant predictive values for the presence of symptomatic stroke among patients with a moderate or higher degree of carotid stenosis.

Dual-mode spatial index modulation for MIMO-OWC.

In this Letter, we propose and demonstrate a dual-mode spatial index modulation (DM-SIM) scheme for spectral efficiency enhancement of band-limited multiple-input multiple-output optical wireless communication (MIMO-OWC) systems. By performing dual-mode index modulation in the spatial domain, DM-SIM can transmit both spatial and constellation symbols. Since constellation design plays a vital role in the proposed DM-SIM scheme, we further propose three dual-mode constellation design approaches including phase rotation, amplitude scaling and joint phase rotation and amplitude scaling. Moreover, we also designed a differential log-likelihood ratio (LLR) detector for the proposed DM-SIM scheme. Experimental results show that the joint phase rotation and amplitude scaling approach can achieve a remarkable 3.2 dB signal-to-noise ratio (SNR) gain compared with the phase rotation approach in a 2×2 MIMO-OWC system applying DM-SIM.

Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a leading life-threatening health challenge worldwide, with pressing needs for novel therapeutic strategies. Sphingosine kinase 1 (SphK1), a well-established pro-cancer enzyme, is aberrantly overexpressed in a multitude of malignancies, including HCC. Our previous research has shown that genetic ablation of Sphk1 mitigates HCC progression in mice. Therefore, the development of PF-543, a highly selective SphK1 inhibitor, opens a new avenue for HCC treatment. However, the anti-cancer efficacy of PF-543 has not yet been investigated in primary cancer models in vivo, thereby limiting its further translation. METHODS: Building upon the identification of the active form of SphK1 as a viable therapeutic target in human HCC specimens, we assessed the capacity of PF-543 in suppressing tumor progression using a diethylnitrosamine-induced mouse model of primary HCC. We further delineated its underlying mechanisms in both HCC and endothelial cells. Key findings were validated in Sphk1 knockout mice and lentiviral-mediated SphK1 knockdown cells. RESULTS: SphK1 activity was found to be elevated in human HCC tissues. Administration of PF-543 effectively abrogated hepatic SphK1 activity and significantly suppressed HCC progression in diethylnitrosamine-treated mice. The primary mechanism of action was through the inhibition of tumor neovascularization, as PF-543 disrupted endothelial cell angiogenesis even in a pro-angiogenic milieu. Mechanistically, PF-543 induced proteasomal degradation of the critical glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, thus restricting the energy supply essential for tumor angiogenesis. These effects of PF-543 could be reversed upon S1P supplementation in an S1P receptor-dependent manner. CONCLUSIONS: This study provides the first in vivo evidence supporting the potential of PF-543 as an effective anti-HCC agent. It also uncovers previously undescribed links between the pro-cancer, pro-angiogenic and pro-glycolytic roles of the SphK1/S1P/S1P receptor axis. Importantly, unlike conventional anti-HCC drugs that target individual pro-angiogenic drivers, PF-543 impairs the PFKFB3-dictated glycolytic energy engine that fuels tumor angiogenesis, representing a novel and potentially safer therapeutic strategy for HCC.

Effect of ticagrelor versus clopidogrel after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome-propensity score matching analysis.

BACKGROUND: The effect of different dual antiplatelet therapies on thrombotic events on the background of intravascular ultrasound (IVUS) guidance is unclear. We investigated whether ticagrelor can provide any additional benefit to clopidogrel in reducing thrombotic events in acute coronary syndrome (ACS) treated with drug- eluting stent (DES), when guided by IVUS or not. METHODS: A total of 5,666 ACS patients who underwent DES implantation and who were discharged on dual antiplatelet therapy were enrolled and grouped according to the use of IVUS or not. Each group was subdivided into two subgroups according to the type of P2Y12 inhibitor used after discharge. Propensity score matching (PSM) was used between the IVUS and no-IVUS groups. Covariate adjustment of Cox proportional hazards model was used between the ticagrelor and clopidogrel groups. Thrombotic event at 12 months was compared in groups separately. RESULTS: After PSM, 12-month follow-up data were available for 1,174 patients. Major adverse cardiac events (MACE) were less frequent in the IVUS-guided group (2.2% vs. 4.3%, P = 0.081) with a trend toward statistical significance. Comparison of antiplatelet regimens revealed significantly fewer major adverse cardiac and cerebrovascular events (MACCE) with ticagrelor in the entire PSM cohort and angiography-guided subgroup (2.9% vs. 5.7%, P = 0.035; 3.1% vs. 6.4%, P = 0.020, respectively). Among patients in the IVUS-guided group the outcome was comparable (2.5% vs. 4.4%, P = 0.312). Ticagrelor was associated with increasing bleeding incidence in the entire PSM cohort (1.3% vs. 3.3%, P = 0.030), mainly due to Bleeding Academic Research Consortium type 2 bleeding (0.7% vs. 2.6%, P = 0.010). The results were consistent after covariate adjustment of Cox proportional hazards model. CONCLUSION: The comparison of ischemic benefit between ticagrelor and clopidogrel was similar in patients receiving IVUS guidance during stent implantation, probably due to the precise implantation of IVUS. Multicenter, randomized studies should be performed to validate this conclusion.

Preparation and photothermal therapy of gold nanorods modified by Belamcanda chinensis (L.) DC polysaccharide.

In recent years, the application of nanoparticles formed by coupling metal nanomaterials of photothermal therapy with polysaccharides as modified carriers in the targeted treatment of liver cancer has attracted extensive attention. In the present work, an undescribed homogeneous polysaccharide BCP50-2 was obtained from Belamcanda chinensis (L.) DC. The structural analysis displayed that BCP50-2 contained galactose and a small amount of arabinose, and was mainly composed of six monosaccharide residues: →3,5)-α-l-Araf-(1→, →4)-ß-d-Galp-(1→, →4,6)-ß-d-Galp-(1→, →3)-α-l-Galp-(1→, terminal α-l-Araf, and terminal ß-d-Galp. To enhance the antitumor activity of BCP50-2, BCP50-2-AuNRs were prepared by coupling BCP50-2 with gold nanorods for the treatment of liver cancer. BCP50-2-AuNRs were rod-shaped with a long diameter of 26.8 nm and had good photothermal conversion effects. Under near-infrared (NIR) light irradiation, BCP50-2-AuNRs possessed photothermal effects and suppressed the growth of HepG2, A549, and MCF-7 cells. In addition, BCP50-2-AuNRs inhibited the development of liver cancer by inducing cell apoptosis, arresting the cell cycle in G2/M phases, and inhibiting cell migration. Moreover, BCP50-2-AuNRs inhibited tumor proliferation, migration, and angiogenesis in zebrafish. In summary, BCP50-2-AuNRs may be potentially useful for cancer treatment.

Efficient and Low-Complex Signal Detection with Iterative Feedback in Wireless MIMO-OFDM Systems.

To solve error propagation and exorbitant computational complexity of signal detection in wireless multiple-input multiple-output-orthogonal frequency division multiplexing (MIMO-OFDM) systems, a low-complex and efficient signal detection with iterative feedback is proposed via a constellation point feedback optimization of minimum mean square error-ordered successive interference cancellation (MMSE-OSIC) to approach the optimal detection. The candidate vectors are formed by selecting the candidate constellation points. Additionally, the vector most approaching received signals is chosen by the maximum likelihood (ML) criterion in formed candidate vectors to reduce the error propagation by previous erroneous decision, thus improving the detection performance. Under a large number of matrix inversion operations in the above iterative MMSE process, effective and fast signal detection is hard to be achieved. Then, a symmetric successive relaxation iterative algorithm is proposed to avoid the complex matrix inversion calculation process. The relaxation factor and initial iteration value are reasonably configured with low computational complexity to achieve good detection close to that of the MMSE with fewer iterations. Simultaneously, the error diffusion and complexity accumulation caused by the successive detection of the subsequent OSIC scheme are also improved. In addition, a method via a parallel coarse and fine detection deals with several layers to both reduce iterations and improve performance. Therefore, the proposed scheme significantly promotes the MIMO-OFDM performance and thus plays an irreplaceable role in the future sixth generation (6G) mobile communications and wireless sensor networks, and so on.

Bidirectional associations between hearing difficulty and cognitive function in Chinese adults: a longitudinal study.

Background: Middle-aged and older adults frequently experience hearing loss and a decline in cognitive function. Although an association between hearing difficulty and cognitive function has been demonstrated, its temporal sequence remains unclear. Therefore, we investigated whether there are bidirectional relationships between hearing difficulty and cognitive function and explored the mediating role of depressive symptoms in this relationship. Method: We used the cross-lagged panel model and the random-intercept cross-lagged panel model to look for any possible two-way link between self-reported hearing difficulty and cognitive function. To investigate depressive symptoms' role in this association, a mediation analysis was conducted. The sample was made up of 4,363 adults aged 45 and above from the China Health and Retirement Longitudinal Study (CHARLS; 2011-2018; 44.83% were women; mean age was 56.16 years). One question was used to determine whether someone had a hearing impairment. The tests of cognitive function included episodic memory and intelligence. The Center for Epidemiologic Studies Depression Scale, which consists of 10 items, was used to measure depressive symptoms. Results: A bidirectional association between hearing and cognition was observed, with cognition predominating (Wald χ2 (1) = 7.241, p < 0.01). At the between-person level, after controlling for potential confounders, worse hearing in 2011 predicted worse cognitive function in 2013 (ß = -0.039, p < 0.01) and vice versa (ß = -0.041, p < 0.01) at the between-person level. Additionally, there was no corresponding cross-lagged effect of cognitive function on hearing difficulty; rather, the more hearing difficulty, the greater the cognitive decline at the within-person level. According to the cross-lagged mediation model, depressive symptoms partially mediates the impact of cognitive function on subsequent hearing difficulty (indirect effect: -0.003, bootstrap 95% confidence interval: -0.005, -0.001, p < 0.05), but not the other way around. Conclusion: These results showed that within-person relationships between hearing impairment and cognitive function were unidirectional, while between-person relationships were reciprocal. Setting mental health first may be able to break the vicious cycle that relates hearing loss to cognitive decline. Comprehensive long-term care requires services that address depressive symptoms and cognitive decline to be integrated with the hearing management.

Pericarotid Fat Stranding at Computed Tomography Angiography: A Marker of the Short-Term Prognosis of Acute Ischemic Stroke.

PURPOSE: Perivascular epicardial fat stranding detected in the coronary computed tomography (CT) angiography is associated with culprit lesions and provides helpful information on the risk of acute coronary syndrome. This study aimed to evaluate the potential clinical significance of pericarotid fat stranding (PCFS) and investigate the association between PCFS and short-term prognosis in acute stroke using head and neck CT angiography (CTA). METHODS: This study included 80 patients (mean age, 69.69 ± 11.03; 58 men) who underwent both head and neck CTA and magnetic resonance imaging within a 1-week period. Baseline characteristics, pericarotid adipose tissue attenuation, plaque characteristics, ischemic penumbra, infarct core volume, infarct core growth rate (CGR), and the grade of collateral status were recorded and compared between a PCFS group and a non-PCFS group. Data were compared using the 2-sample t test, Mann-Whitney U test, Fisher exact test, and Spearman rank correlation analysis. RESULTS: We found that patients with PCFS had a significantly higher pericarotid adipose tissue density than patients without PCFS (-55.75 ± 5.53 vs -65.82 ± 9.65, P < 0.001). Patients with PCFS showed a larger infarct core volume (166.43 ± 73.07 vs 91.43 ± 55.03, P = 0.001) and faster CGR (39.57 ± 12.01 vs 19.83 ± 32.77; P < 0.001), and the frequency of adverse prognosis was more significant than in control participants (83.33% vs 19.11%). CONCLUSIONS: Individuals with PCFS showed higher CGR, which was substantially related to worse outcomes in patients with acute stroke with ipsilateral carotid atherosclerosis. Recognition of PCFS may help predict stroke prognosis and allow doctors to take early action to improve patient prognosis.

Improved Frequency Domain Turbo Equalization with Expectation Propagation Interference Cancellation in Underwater Acoustic Communications.

This paper proposes an improved frequency domain turbo equalization (IFDTE) with iterative channel estimation and feedback to achieve both a good performance and low complexity in underwater acoustic communications (UWACs). A selective zero-attracting (SZA) improved proportionate normal least mean square (SZA-IPNLMS) algorithm is adopted by utilizing the sparsity of the UWAC channel to estimate it using a training sequence. Simultaneously, a set-membership (SM) SZA differential IPNLMS (SM SZA-DIPNLMS) with variable step size is adopted to estimate the channel status information (CSI) in the iterative channel estimation with soft feedback. In this way, the computational complexity for iterative channel estimation is reduced effectively with minimal performance loss. Different from traditional schemes in UWACs, an IFDTE with expectation propagation (EP) interference cancellation is adopted to estimate the a posteriori probability of transmitted symbols iteratively. A bidirectional IFDTE with the EP interference cancellation is proposed to further accelerate the convergence. THe simulation results show that the proposed channel estimation obtains 1.9 and 0.5 dB performance gains, when compared with those of the IPNLMS and the l0-IPNLMS at a bit error rate (BER) of 10-3. The proposed channel estimation also effectively reduces the unnecessary updating of the coefficients of the UWAC channel. Compared with traditional time-domain turbo equalization and FDTE in UWACs, the IFDTE obtains 0.5 and 1 dB gains in the environment of SPACE'08 and it obtains 0.5 and 0.4 dB gains in the environment of MACE'04 at a BER of 10-3. Therefore, the proposed scheme obtains a good BER performance and low complexity and it is suitable for efficient use in UWACs.

Dual functionalized hyaluronic acid micelles loading paclitaxel for the therapy of breast cancer.

Although many carriers for the delivery of chemotherapeutic drugs have been investigated, the disadvantages of passive targeting and uncontrolled drug release limit their utility. Herein, hyaluronic acid (HA) was hydrophobically modified to serve as a carrier for binding to cluster determinant 44 (CD44) overexpressed on tumor cell surfaces. Specifically, after deacetylation, HA was grafted to dodecylamine or tetradecylamine to afford amphiphilic zwitterionic polymer micelles, designated dHAD and dHAT, respectively, for the delivery of paclitaxel (PTX). The micelles were negatively charged at pH 7.4 and positively charged at pH 5.6, and this pH sensitivity facilitated PTX release under acidic conditions. The cell uptake efficiencies of the dHAD-PTX and dHAT-PTX micelles by MCF-7 cells after 4 h of incubation were 96.9% and 95.4%, respectively, and their affinities for CD44 were twice that of HA. Furthermore, the micelles markedly inhibited tumor growth both in vitro and in vivo, with IC50 values of 1.943 µg/mL for dHAD-PTX and 1.874 µg/mL for dHAT-PTX for MCF-7 cells; the tumor inhibition rate of dHAD-PTX (92.96%) was higher than that of dHAT-PTX (78.65%). Importantly, dHAD and dHAT micelles showed negligible systemic toxicity. Our findings suggest that these micelles are promising delivery vehicles for antitumor drugs.