Phytosterols in human serum as measured using a liquid chromatography tandem mass spectrometry.

Phytosterols are lipophilic compounds found in plants with structural similarity to mammalian cholesterol. They cannot be endogenously produced by mammals and therefore always originate from diet. There has been increased interest in dietary phytosterols over the last few decades due to their association with a variety of beneficial health effects including low-density lipoprotein cholesterol lowering, anti-inflammatory and anti-cancerous effects. They are proposed as potential moderators for diseases associated with the central nervous system where cholesterol homeostasis is found to be imperative (multiple sclerosis, dementia, etc.) due to their ability to reach the brain. Here we utilised an enzyme-assisted derivatisation for sterol analysis (EADSA) in combination with a liquid chromatography tandem mass spectrometry (LC-MSn) to characterise phytosterol content in human serum. As little as 100 fg of plant sterol was injected on a reversed phase LC column. The method allows semi-quantitative measurements of phytosterols and their derivatives simultaneously with measurement of cholesterol metabolites. The identification of phytosterols in human serum was based on comparison of their LC retention times and MS2, MS3 spectra with a library of authentic standards. Free campesterol serum concentration was in the range from 0.30 - 4.10µg/mL, ß-sitosterol 0.16 - 3.37µg/mL and fucosterol was at lowest concentration range from 0.05 - 0.38µg/mL in ten individuals. This analytical methodology could be applied to the analysis of other biological fluids and tissues.

Five-year survival prognosis of young, middle-aged, and elderly adult female invasive breast cancer patients by clinical and lifestyle characteristics.

PURPOSE: Early-onset breast cancer incidence has been increasing globally and in Taiwan. However, previous studies have not comprehensively examined how clinical and lifestyle characteristics influence the 5-year survival of breast cancer diagnosed at different stages of adulthood. METHODS: We analyzed the Taiwan National Cancer Registry and Cause of Death datasets to understand how clinical factors (including tumor and treatment characteristics) and lifestyle factors (including body mass index, cigarette smoking, and alcohol consumption) were associated with the 5-year survival of 8471 young, 57,695 middle-aged, and 14,074 elderly female adult invasive breast cancer patients respectively diagnosed at age 20-39, 40-64, and ≥ 65 years between 2002 and 2015, with mortality follow-up to 2020. Poisson regression was used for obtaining the crude and adjusted 5-year survival risk ratios. RESULTS: Clinical and lifestyle characteristics were distributed differently but had mostly similar direction of association with 5-year survival for the three age groups. Receiving any treatment was associated with better survival, especially for elderly patients. Being underweight at initial cancer treatment was associated with worse survival than having normal weight, especially for elderly patients. Current smokers had worse survival than never smokers for middle-aged and elderly patients. The 5-year breast cancer-specific survival was not significantly higher for those of age 45-49 years than 40-44 years, despite the recommended starting screening age is 45 years in Taiwan. CONCLUSION: Our findings contribute to the understanding of early-onset and later-onset female breast cancer characteristics and prognosis, which may inform surveillance and treatment strategies to achieve better breast cancer prognosis.

Combining a glycolysis­related prognostic model based on scRNA­Seq with experimental verification identifies ZFP41 as a potential prognostic biomarker for HCC.

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis, and its heterogeneity affects the response to clinical treatments. Glycolysis is highly associated with HCC therapy and prognosis. The present study aimed to identify a novel biomarker for HCC by exploring the heterogeneity of glycolysis in HCC. The intersection of both marker genes of glycolysis­related cell clusters from single­cell RNA sequencing analysis and mRNA data of liver HCC from The Cancer Genome Atlas were used to construct a prognostic model through Cox proportional hazard regression and the least absolute shrinkage and selection operator Cox regression. Data from the International Cancer Genome Consortium were used to validate the results of the analysis. Immune status analysis was then conducted. A significant gene in the prognostic model was identified as a potential biomarker and was verified through in vitro experiments. The results revealed that the glycolysis­related prognostic model divided patients with HCC into high­ and low­risk groups. A nomogram combining the model and clinical features exhibited accurate predictive ability, with an area under the curve of 0.763 at 3 years. The high­risk group exhibited a higher expression of checkpoint genes and lower tumor immune dysfunction and exclusion scores, suggesting that this group may be more likely to benefit from immunotherapy. The tumor tissues had a higher zinc finger protein (ZFP)41 mRNA and protein expression compared with the adjacent tissues. In vitro analyses revealed that ZFP41 played a crucial role in cell viability, proliferation, migration, invasion and glycolysis. On the whole, the present study demonstrates that the glycolysis­related prognostic gene, ZFP41, is a potential prognostic biomarker and therapeutic target, and may play a crucial role in glycolysis and malignancy in HCC.

A Real-World Experience on a Chinese Population of Patients With Unresectable Hepatocellular Carcinoma Treated With Nivolumab.

Background: For unresectable hepatocellular carcinoma (HCC), nivolumab (anti-programmed death receptor-1 (PD-1)) is used as non-curative interventions. The aim of the study was to focus on the real-world experience of nivolumab applied to patients with HCC. Methods: Unresectable HCC patients receiving nivolumab treatments at Taichung Veterans General Hospital, from June 2018 to May 2020, were recruited. Exclusion criteria were Child-Pugh stage C, poor performance status, a lack of compliance or intolerable to drug treatments. The tumor radiological responses and survival outcomes of enrolled patients were collected and analyzed. Results: Among a total of 57 patients, most of them were classified as Child-Pugh stage A (70.2%) and Barcelona Clinic Liver Cancer (BCLC) stage C (66.7%). Nivolumab was given to 14 (24.6%) as the primary-line, and 43 patients (75.4%) as the secondary-line systemic treatments. The mean therapeutic duration was 6.5 months. Objective response rate (ORR) was 24.6%, and disease control rate (DCR) was 42.1%. The overall median progression-free survival (PFS) was 5.8 months (95% confidence interval (CI): 1.1 - 10.6), and overall survival (OS) was 11.5 months (95% CI: 4.3 - 17.8). Immune-related adverse event (IRAE) was 8.8%. Presence of alpha-fetoprotein (AFP) response (a decline in AFP ≥ 10% from baseline) during therapy predicted the tumor radiological response (to objective response: hazard ratio (HR): 4.89, 95% CI: 1.14 - 21.00; to disease control: HR: 4.71, 95% CI: 1.32 - 16.81). Those with tumor radiological responses showed longer PFS and OS. Conclusions: Decline in AFP during therapy has a predicting role on HCC radiological responses to nivolumab. Achieving radiological responses had better survival outcomes.

Hepatitis C virus antibody seropositivity is associated with albuminuria but not peripheral artery disease in patients with type 2 diabetes.

Hepatitis C virus (HCV) infection is prevalent in patients with type 2 diabetes mellitus (DM). We aimed to investigate whether HCV antibody (Ab) seropositivity is associated with diabetic micro- and macro-vascular diseases. In this hospital-based cross-sectional study, we retrospectively collected data from patients who participated in the diabetes pay-for-performance program and underwent HCV Ab screening in the annual comprehensive assessment between January 2021 and March 2022. We examined the relationships of HCV Ab seropositivity with the spot urinary albumin-to-creatinine ratio (UACR) and ankle-brachial index (ABI) in patients aged ≥ 50 years with type 2 DM. A total of 1758 patients were enrolled, and 85 (4.83%) of the enrolled patients had HCV Ab seropositivity. Multivariable regression analyses revealed that albuminuria showed a dose-dependent association with HCV Ab seropositivity (UACR [30-299 mg/g]: odds ratio [OR] = 1.463, 95% confidence interval [CI] 0.872‒2.456); UACR [≥ 300 mg/g]: OR = 2.300, 95% CI 1.160‒4.562; P for trend = 0.015) when compared with normal albuminuria (UACR < 30 mg/g). However, the proportion of patients with peripheral arterial disease, defined as an ABI ≤ 0.9, was not significantly different between the groups with and without HCV Ab seropositivity (3.5% vs. 3.9%, P = 0.999). In conclusion, severely increased albuminuria, but not the ABI, showed a significant association with HCV Ab seropositivity in patients aged ≥ 50 years with type 2 DM.

Comprehensive analysis of pain genes in prognosis of kidney renal clear cell carcinoma and tumor immunotherapy: A comprehensive bioinformatic study.

Background: The effect of pain genes (NAV1, EHMT2, SP1, SLC6A4, COMT, OPRM1, OPRD1, CYP2D6, and CYP3A4) have not been reported previously in kidney renal clear cell carcinoma (KIRC) patients and thus we made a comprehensive analysis of pain genes in the prognosis of KIRC and tumor immunotherapy. Methods: In this study, TCGA, Kaplan-Meier plotter, Metascape, STRING, Human Protein Atlas, Single Cell Expression Atlas database, LinkedOmics, cBioPortal, MethSurv, CancerSEA, COSMIC database and R package (ggplot2, version 3.3.3) were used for comprehensive analysis of pain genes in KIRC. Pearson and Spearman correlation coefficients were for co-expression analysis. Immunotherapy and TISIDB database were used for tumor Immunotherapy. Results: Representative pain genes (SP1, SLC6A4, COMT, OPRD1, CYP2D6, and CYP3A4) were statistically significant (p < 0.0001) in the prognosis of KIRC. Immunotherapy (anti-PD-1 therapy, anti-PD-L1 therapy, and anti-CTLA4 therapy) and immunomodulator (immunoinhibitor, immunostimulator, and MHC molecule) in KIRC were significant associated with pain genes (SP1, SLC6A4, COMT, OPRD1, CYP2D6, and CYP3A4), which were the important addition to clinical decision making for patients. Conclusions: Our study uncovered a mechanism for the effect of pain genes on KIRC outcome via the modulation of associated co-expression gene networks, gene variation, and tumor Immunotherapy.

Tensor Robust Kernel PCA for Multidimensional Data.

Recently, the tensor nuclear norm (TNN)-based tensor robust principle component analysis (TRPCA) has achieved impressive performance in multidimensional data processing. The underlying assumption in TNN is the low-rankness of frontal slices of the tensor in the transformed domain (e.g., Fourier domain). However, the low-rankness assumption is usually violative for real-world multidimensional data (e.g., video and image) due to their intrinsically nonlinear structure. How to effectively and efficiently exploit the intrinsic structure of multidimensional data remains a challenge. In this article, we first suggest a kernelized TNN (KTNN) by leveraging the nonlinear kernel mapping in the transform domain, which faithfully captures the intrinsic structure (i.e., implicit low-rankness) of multidimensional data and is computed at a lower cost by introducing kernel trick. Armed with KTNN, we propose a tensor robust kernel PCA (TRKPCA) model for handling multidimensional data, which decomposes the observed tensor into an implicit low-rank component and a sparse component. To tackle the nonlinear and nonconvex model, we develop an efficient alternating direction method of multipliers (ADMM)-based algorithm. Extensive experiments on real-world applications collectively verify that TRKPCA achieves superiority over the state-of-the-art RPCA methods.

Interfacial Electron Transfer in PbI2@Single-Walled Carbon Nanotube van der Waals Heterostructures for High-Stability Self-Powered Photodetectors.

Acquiring a deep insight into the electron transfer mechanism and applications of one-dimensional (1D) van der Waals heterostructures (vdWHs) has always been a significant challenge. Herein, through direct observation using aberration-corrected transmission electron microscopy (AC-TEM), we verify the stable formation of a high-quality 1D heterostructure composed of PbI2@single-walled carbon nanotubes (SWCNTs). The phenomenon of electron transfer between PbI2 and SWCNT is elucidated through spectroscopic investigations, including Raman and X-ray photoelectron spectroscopy (XPS). Electrochemical testing indicates the electron transfer and enduring stability of 1D PbI2 within SWCNTs. Moreover, leveraging the aforementioned electron transfer mechanism, we engineer self-powered photodetectors that exhibit exceptional photocurrent and a 3-order-of-magnitude switching ratio. Subsequently, we reveal its unique electron transfer behavior using Kelvin probe force microscopic (KPFM) tests. According to KPFM, the average surface potential of SWCNTs decreases by 80.6 mV after filling. Theoretical calculations illustrate a charge transfer of 0.02 e per unit cell. This work provides an effective strategy for the in-depth investigation and application of electron transfer in 1D vdWHs.

Reinforcement learning-based adaptive beam alignment in a photodiode-integrated array antenna module.

We successfully demonstrated an intelligent adaptive beam alignment scheme using a reinforcement learning (RL) algorithm integrated with an 8 × 8 photonic array antenna operating in the 40 GHz millimeter wave (MMW) band. In our proposed scheme, the three key elements of RL: state, action, and reward, are represented as the phase values in the photonic array antenna, phase changes with specified steps, and an obtained error vector magnitude (EVM) value, respectively. Furthermore, thanks to the Q-table, the RL agent can effectively choose the most suitable action based on its prior experiences. As a result, the proposed scheme autonomously achieves the best EVM performance by determining the optimal phase. In this Letter, we verify the capability of the proposed scheme in single- and multiple-user scenarios and experimentally demonstrate the performance of beam alignment to the user's location optimized by the RL algorithm. The achieved results always meet the signal quality requirement specified by the 3rd Generation Partnership Project (3GPP) criterion for 64-QAM orthogonal frequency division multiplexing (OFDM).

New HIV Infections Among Key Populations and Their Partners in 2010 and 2022, by World Region: A Multisources Estimation.

BACKGROUND: Previously, The Joint United Nations Programme on HIV/AIDS estimated proportions of adult new HIV infections among key populations (KPs) in the last calendar year, globally and in 8 regions. We refined and updated these, for 2010 and 2022, using country-level trend models informed by national data. METHODS: Infections among 15-49 year olds were estimated for sex workers (SWs), male clients of female SW, men who have sex with men (MSM), people who inject drugs (PWID), transgender women (TGW), and non-KP sex partners of these groups. Transmission models used were Goals (71 countries), AIDS Epidemic Model (13 Asian countries), Optima (9 European and Central Asian countries), and Thembisa (South Africa). Statistical Estimation and Projection Package fits were used for 15 countries. For 40 countries, new infections in 1 or more KPs were approximated from first-time diagnoses by the mode of transmission. Infection proportions among nonclient partners came from Goals, Optima, AIDS Epidemic Model, and Thembisa. For remaining countries and groups not represented in models, median proportions by KP were extrapolated from countries modeled within the same region. RESULTS: Across 172 countries, estimated proportions of new adult infections in 2010 and 2022 were both 7.7% for SW, 11% and 20% for MSM, 0.72% and 1.1% for TGW, 6.8% and 8.0% for PWID, 12% and 10% for clients, and 5.3% and 8.2% for nonclient partners. In sub-Saharan Africa, proportions of new HIV infections decreased among SW, clients, and non-KP partners but increased for PWID; elsewhere these groups' 2010-to-2022 differences were opposite. For MSM and TGW, the proportions increased across all regions. CONCLUSIONS: KPs continue to have disproportionately high HIV incidence.

Comparison of Empirically Derived and Model-Based Estimates of Key Population HIV Incidence and the Distribution of New Infections by Population Group in Sub-Saharan Africa.

BACKGROUND: The distribution of new HIV infections among key populations, including female sex workers (FSWs), gay men and other men who have sex with men (MSM), and people who inject drugs (PWID) are essential information to guide an HIV response, but data are limited in sub-Saharan Africa (SSA). We analyzed empirically derived and mathematical model-based estimates of HIV incidence among key populations and compared with the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates. METHODS: We estimated HIV incidence among FSW and MSM in SSA by combining meta-analyses of empirical key population HIV incidence relative to the total population incidence with key population size estimates (KPSE) and HIV prevalence. Dynamic HIV transmission model estimates of HIV incidence and percentage of new infections among key populations were extracted from 94 country applications of 9 mathematical models. We compared these with UNAIDS-reported distribution of new infections, implied key population HIV incidence and incidence-to-prevalence ratios. RESULTS: Across SSA, empirical FSW HIV incidence was 8.6-fold (95% confidence interval: 5.7 to 12.9) higher than total population female 15-39 year incidence, and MSM HIV incidence was 41.8-fold (95% confidence interval: 21.9 to 79.6) male 15-29 year incidence. Combined with KPSE, these implied 12% of new HIV infections in 2021 were among FSW and MSM (5% and 7% respectively). In sensitivity analysis varying KPSE proportions within 95% uncertainty range, the proportion of new infections among FSW and MSM was between 9% and 19%. Insufficient data were available to estimate PWID incidence rate ratios. Across 94 models, median proportion of new infections among FSW, MSM, and PWID was 6.4% (interquartile range 3.2%-11.7%), both much lower than the 25% reported by UNAIDS. CONCLUSION: Empirically derived and model-based estimates of HIV incidence confirm dramatically higher HIV risk among key populations in SSA. Estimated proportions of new infections among key populations in 2021 were sensitive to population size assumptions and were substantially lower than estimates reported by UNAIDS.

Measuring HIV Acquisitions Among Partners of Key Populations: Estimates From HIV Transmission Dynamic Models.

BACKGROUND: Key populations (KPs), including female sex workers (FSWs), gay men and other men who have sex with men (MSM), people who inject drugs (PWID), and transgender women (TGW) experience disproportionate risks of HIV acquisition. The UNAIDS Global AIDS 2022 Update reported that one-quarter of all new HIV infections occurred among their non-KP sexual partners. However, this fraction relied on heuristics regarding the ratio of new infections that KPs transmitted to their non-KP partners to the new infections acquired among KPs (herein referred to as "infection ratios"). We recalculated these ratios using dynamic transmission models. SETTING: One hundred seventy-eight settings (106 countries). METHODS: Infection ratios for FSW, MSM, PWID, TGW, and clients of FSW were estimated from 12 models for 2020. RESULTS: Median model estimates of infection ratios were 0.7 (interquartile range: 0.5-1.0; n = 172 estimates) and 1.2 (0.8-1.8; n = 127) for acquisitions from FSW clients and transmissions from FSW to all their non-KP partners, respectively, which were comparable with the previous UNAIDS assumptions (0.2-1.5 across regions). Model estimates for female partners of MSM were 0.5 (0.2-0.8; n = 20) and 0.3 (0.2-0.4; n = 10) for partners of PWID across settings in Eastern and Southern Africa, lower than the corresponding UNAIDS assumptions (0.9 and 0.8, respectively). The few available model estimates for TGW were higher [5.1 (1.2-7.0; n = 8)] than the UNAIDS assumptions (0.1-0.3). Model estimates for non-FSW partners of FSW clients in Western and Central Africa were high (1.7; 1.0-2.3; n = 29). CONCLUSIONS: Ratios of new infections among non-KP partners relative to KP were high, confirming the importance of better addressing prevention and treatment needs among KP as central to reducing overall HIV incidence.

Interlayer Charge Transfer Induced Electrical Behavior Transition in 1D AgI@sSWCNT van der Waals Heterostructures.

The emergence of one-dimensional van der Waals heterostructures (1D vdWHs) opens up potential fields with unique properties, but precise synthesis remains a challenge. The utilization of mixed conductive types of carbon nanotubes as templates has imposed restrictions on the investigation of the electrical behavior and interlayer interaction of 1D vdWHs. In this study, we efficiently encapsulated silver iodide in high-purity semiconducting single-walled carbon nanotubes (sSWCNTs), forming 1D AgI@sSWCNT vdWHs. We characterized the semiconductor-metal transition and increased the carrier concentration of individual AgI@sSWCNTs via sensitive dielectric force microscopy and confirmed the results through electrical device tests. The electrical behavior transition was attributed to an interlayer charge transfer, as demonstrated by Kelvin probe force microscopy. Furthermore, we showed that this method of synthesizing 1D heterostructures can be extended to other metal halides. This work opens the door for the further exploration of the electrical properties of 1D vdWHs.

Cancer burden and risk in the Chinese population aged 55 years and above: A systematic analysis and comparison with the USA and Western Europe.

Background: We analysed the cancer burden among elderly Chinese people over the age of 55 years and compared them to USA and Western Europe to explore the cancer model in China. Methods: We retrieved data on 29 cancers with 34 risk factors from the 2019 Global Burden of Disease database to evaluate the cancer burden in Chinese elderly individuals aged 55 years and older. We then used the age-standardised incidence rate (ASIR), age-standardised death rate (ASDR), age-standardised disability-adjusted life year (DALY) rate, and average annual percentage change (AAPC) to compare the characteristics and change trend of cancers among China, USA, and Western Europe. Results: In 2019, the number of incident cases of 29 cancers among people aged 55 years and above in China increased more than 3-fold compared to 1990, while the number of deaths and DALYs approximately doubled. We also found that the cancer population in China was ageing; meanwhile, the cancer burden became significantly higher for men than for women, and the gap between men and women had widened. Cancers with the highest cancer DALYs were lung cancer (13 444 500; 95% uncertainty interval (UI) = 11 307 100, 15 853 700), stomach cancer (7 303 900; 95% UI = 6 094 600, 8 586 500), oesophageal cancer (4 633 500; 95% UI = 3 642 500, 5 601 200), colon and rectum cancer (4 386 500; 95% UI = 3 769 500, 5 067 200), liver cancer (2 915 100, 95% UI = 2 456 300, 3 463 900), and pancreatic cancer (2 028 400; 95% UI = 1 725 000, 2 354 900). Compared with 1990, the DALY rate and incidence rate of stomach cancer, oesophageal cancer, and liver cancer had markedly decreased. The DALY rate and incidence rate of lung, colon, rectum, and pancreatic cancer had increased significantly, as did the incidence rate of breast cancer in women. Smoking and diet were the top two cancer risk factors, and the impact of ambient particulate matter pollution on cancer increased each year. The overall 29 cancers age-standardised DALY rate and ASDR in China, USA, and Western Europe were similar, and all showed downward trend in the past 30 years. Compared with the USA and Western Europe, the age-standardised DALY rate of liver, nasopharyngeal, oesophageal, stomach, and cervical cancers in China was more prominent. The age-standardised DALY rate of lung cancer and colon and rectum cancer decreased annually in Western Europe and the USA, but increased in China. Conclusions: Over the past 30 years, China had made progress in controlling stomach, oesophageal, and liver cancer. However, lung, colon, rectum, pancreatic, and breast cancers had become more prevalent, having risen alongside economic development. The risks of smoking and dietary were major issues that need to be addressed urgently. The cancer situation in China remains serious; future cancer prevention efforts need to balance economic development with people's physical health, identify key groups, improve the health environment of residents and guide them to live a healthy life, and expand the scope of cancer screening.

Trapdoor Deformity Correction Post Nasal Bilobed Flaps for Basal Cell Carcinoma Reconstruction With Multiple Laser Modalities.

ABSTRACT: In case of excision of nasal basal cell carcinoma (BCC), bilobed flaps are considered the criterion standard of reconstruction for defect less than 15 mm in size. However, there is still a risk of trapdoor deformity formation, of which its treatment is less discussed. A 44-year-old woman who was diagnosed with nasal BCC and underwent tumor excision with bilobed flap reconstruction presented with trapdoor deformity postoperatively. The computed Vancouver Scar Scale was 7. After early intervention of multiple laser modalities, including 2 sessions of 585-nm pulsed dye laser with a fluence of 9 J/cm2, pulse duration of 6 milliseconds, and spot size of 6 mm, 2940-nm Er-yttrium aluminum garnet (YAG) laser with a pulse energy of 800-900 mJ, repetition rate of 8-9 Hz, and laser spot size of 3-7 mm, and 5 sessions of 1064-nm Nd:YAG fractional picosecond laser with a pulse energy of 2.30-2.70 mJ, repetition rate of 8 Hz, and laser spot size of 6 mm from 5 to 23 weeks postoperatively, the Vancouver Scar Scale score improved to 1, with significant reduction of trapdoor scar erythema and puffiness. Although BCC is often curable, tumor excision causes unsatisfactory appearance satisfaction problem, owing to the apparent location of the lesion. Factors, such as sebaceous tissue thickness, reconstruction over multiple aesthetic subunits of nose, and damage to nasal cartilage framework structure during tumor removal, may increase the risk of trapdoor formation. Early intervention with multiple laser treatment can significantly revise the deformity.

Gastroesophageal Reflux Disease and Rhinosinusitis: A Bidirectional Mendelian Randomization Study.

INTRODUCTION: Comorbidities, such as gastroesophageal reflux disease (GERD), are common in patients with rhinosinusitis (RS). However, the link between RS and GERD has not been fully understood. This study aimed to investigate the causal relationship between GERD and acute (ARS) or chronic RS (CRS), providing references for the pathogenesis and management of RS. METHODS: The data were obtained from the Integrative Epidemiology Unit Open GWAS project and FinnGen. A total of 972,838 individuals were included. The inverse variance-weighted (IVW) method was applied to obtain the primary results of the study. Weighted median, MR-Egger, and mode-based methods were used to determine the robustness of the results. Cochran's Q statistic and MR-Egger method were applied to detect heterogeneity and pleiotrophy in instrumental variables (IVs). Other sensitivity analyses included MR-PRESSO and leave-one-out analysis. RESULTS: The MR study showed that GERD was associated with an increased risk of CRS (OR: 1.36, 95% CI: 1.18-1.57, p < 0.001). The results of other analysis methods were broadly consistent with the IVW estimate. No heterogeneity was detected by Cochran's Q test (p = 0.061) and MR-PRESSO (p = 0.074). No horizontal pleiotropy was shown in IVs (p = 0.700). GERD was also associated with an increased risk of ARS (OR: 1.31, 95% CI: 1.17-1.48, p < 0.001). Some analytical results were inconsistent with the IVW estimate. No heterogeneity and pleiotropy were observed. There was no sufficient evidence for a reverse causal effect of RS on GERD. CONCLUSION: Our study supported that GERD promoted the risk of CRS and may be a potential risk factor for ARS. This provides additional support for further investigation into the mechanisms of GERD on RS.

Constructing asymmetric gradient structures to enhance the energy storage performance of PEI-based composite dielectrics.

Enhancing the high electric field resistance and energy storage capacity of polymer dielectrics has been a long-standing challenge for the iterations of power equipment. Synergistic inhibition of carrier injection and transport is vital to energy storage performance improvement. Herein, promising polymer polyetherimide (PEI) was employed as a matrix and wider bandgap boron nitride nanosheets (BNNSs) were used as a reinforcing filler. Utilizing high-throughput stochastic breakdown simulations with the distribution characteristics of BNNSs as parameters, a series of topological gradient structures with the potential to enhance performance were obtained, thereby shortening the experimental cycle. Changing the BNNS distribution of symmetric/asymmetric and positive/inverse gradients, as well as the total and gradient contents of BNNSs, means that the position and condition of the surface barrier layer and central hinder layer change, which influences the energy storage performance of the polymer at room temperature and high temperature. Remarkably, the asymmetric gradient structure composite dielectrics exhibited excellent performances. Among them, the PEI-based composite dielectric with 2 vol% BNNS asymmetric inverse gradient distribution (gradient content of 1 vol%) achieved energy densities of 8.26 and 4.78 J cm-3 at room temperature and 150 °C, respectively. The asymmetric gradient structure design strategy holds great promise for optimizing the energy storage capacity of polymer dielectric capacitors.

Effectiveness and pharmacological mechanisms of Chinese herbal medicine for coronary heart disease complicated with heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) is widely used for treating coronary heart disease complicated with heart failure (CHD-HF). However, the exact mechanisms involved are still not fully understood. AIM OF THE STUDY: To assess the clinical effectiveness and potential pharmacological mechanisms of CHM for treating CHD-HF. METHODS: Eight databases were retrieved for Randomized Controlled Trials of CHM for CHD-HF published from their inception to March 2023. Quality assessment of include studies was performed by the Cochrane risk-of-bias. Meta-analysis was used to assess the effectiveness of CHM for CHD-HF, and then core drugs and active ingredients were selected by data mining and network pharmacology. Finally, cluster and enrichment analysis were adopted to explore the potential targets and signaling pathways. RESULTS: A total of 52 studies enrolling 5216 patients were included. Meta-analysis revealed that CHM treatment groups significantly improved left ventricular ejection fraction (LVEF), 6-min walk test (6-MWT), left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic diameter (LVESD) than control groups: [LVEF: SMD = 0.7, 95%CI (0.54, 0.87), p < 0.00001, I2 = 80%; 6-MWT: SMD = 0.72, 95%CI (0.58, 0.86), p < 0.0001, I2 = 67%; LVEDD: SMD = -0.79, 95%CI (-0.89, -0.69), p < 0.0001, I2 = 49%; LVESD: SMD = -0.6 (-0.74, -0.46), p < 0.0001, I2 = 0%]. The results of various biological information analysis showed the internal relationship between prescriptions, core drugs, active ingredients and therapeutic targets. Twelve core herbs with the most commonly use and high correlation were selected from 110 CHMs of 52 prescriptions for CHD-HF treatment, and further 65 effective components were screened out according to the most strength value, which were divided into 12 compounds such as terpenoids, flavonoids, steroids and alkaloids and etc. At the same time, 67 therapeutic targets of active ingredients in CHD-HF were filtrated. On these bases, cluster and enrichment analysis of the components and targets were used to explore relevant pharmacological mechanisms, mainly including anti-myocardial cell damage, anti-inflammation, anti-apoptosis, anti-fibrosis, regulation of oxidative stress, anticoagulation and angiogenesis, and improvement of glucose and fatty acid metabolism. CONCLUSION: CHM are effective in treating CHD-HF compared with conventional treatment. Some of the included studies have high risks in the implementation of blinding, so more high-quality studies are needed. The active ingredients of CHM could protect the myocardium and improve pathological environment of CHD-HF in various ways. And CHM has the advantage of multi-component and multi-target treatment for complex diseases.

Cognitive impairment is associated with BDNF-TrkB signaling mediating synaptic damage and reduction of amino acid neurotransmitters in heart failure.

Heart failure (HF) is often accompanied by cognitive impairment (CI). Brain-derived neurotrophic factor (BDNF) deficiency is closely associated with CI. However, the role and mechanism of BDNF in HF with CI is still not fully understood. Here, the case-control study was designed including 25 HF without CI patients (HF-NCI) and 50 HF with CI patients (HF-CI) to investigate the predictive value of BDNF in HF-CI while animal and cell experiments were used for mechanism research. Results found that BDNF levels in serum neuronal-derived exosomes were downregulated in HF-CI patients. There was no significant difference in serum BDNF levels among the two groups. HF rats showed obvious impairment in learning and memory; also, they had reduced thickness and length of postsynaptic density (PSD) and increased synaptic cleft width. Expression of BDNF, TrkB, PSD95, and VGLUT1 was significantly decreased in HF rats brain. In addition, compared with sham rats, amino acids were significantly reduced with no changes in the acetylcholine and monoamine neurotransmitters. Further examination showed that the number of synaptic bifurcations and the expression of BDNF, TrkB, PSD95, and VGLUT1 were all decreased in the neurons that interfered with BDNF-siRNA compared with those in the negative control neurons. Together, our results demonstrated that neuronal-derived exosomal BDNF act as effective biomarkers for prediction of HF-CI. The decrease of BDNF in the brain triggers synaptic structural damage and a decline in amino acid neurotransmitters via the BDNF-TrkB-PSD95/VGLUT1 pathway. This discovery unveils a novel pathological mechanism underlying cognitive impairment following heart failure.

The burden of brain and central nervous system cancers in Asia from 1990 to 2019 and its predicted level in the next twenty-five years : Burden and prediction model of CNS cancers in Asia.

BACKGROUND: Primary brain and central nervous system cancer (collectively called CNS cancers) cause a significant burden to society. The purpose of this study was to evaluate the trends in the burden of CNS cancers from 1990 to 2019 and to predict the incidence and mortality rates and the corresponding numbers for the next 25 years to help countries to understand the trends in its incidence and mortality, and to make better adjustments or formulation of policies and allocation of resources thereby reducing the burden of the disease. METHODS: The 2019 Global Burden of Disease Study provided incidence rates, death rates, and disability-adjusted life year (DALY) data in Asia from 1990 to 2019. To reflect the trends in the age-standardized incidence, mortality, and DALY rates, the estimated annual percentage change (EAPC) was determined. The Bayesian age-period cohort (BAPC) model was employed to predict the burden of CNS cancers in the next 25 years. RESULTS: The incidence, death, and DALY rates of CNS cancers all increased from 1990 to 2019. The age-standardized incidence rate (ASIR) for CNS cancers increased from 9.89/100,000 in 1990 to 12.14/100,000 in 2019, with an EAPC of 0.69 (95% confidence interval (CI): 0.65, 0.73). The ASDR and the age-standardized DALY rate both decreased, with EAPCs of - 0.08 and - 0.52, respectively. Before 2005, the age-standardized DALY rate in East Asia was much greater in females than in males, while in Central Asia, the age-standardized death and DALY rates in males both increased sharply after 2000. In contrast to 1990, the caseload increased for the 55-70 years age group. The number of deaths decreased sharply among individuals aged younger than 20 years, especially in East Asia, accounting for only 5.41% of all deaths. The age group with the highest mortality rate was > 60 years, especially in Japan. The ASIR will continue to increase in Asia from 2020 to 2044, and the ASDR will gradually diminish. The incidence and number of deaths from CNS cancers in Asia are expected to increase over the next 25 years, especially among females. CONCLUSIONS: The study identified an increasing trend in morbidity, mortality and disability-adjusted life-years (DALYs), with differences in age-standardized morbidity rates for different population groups. In addition, it is noteworthy that the burden of disease (as measured by disability-adjusted life-years (DALYs)) is higher among women in Central Asia compared with other regions. ASIR will continue to increase over the next 25 years, with the increase in female cases and mortality expected to be more pronounced. This may need to be further substantiated by additional research, on the basis of which health authorities and policymakers can better utilize limited resources and develop appropriate policies and preventive measures.