Modifiable risk factors and metabolic health in risk of cardiovascular disease among US adults: A nationwide cross-sectional study.

Background: Metabolic syndrome (MetS) could increase the risk of cardiovascular disease (CVD) by 2-fold. Ideal control of modifiable risk factors in Life's Simple 7 (LS7) could reduce the CVD risk among the general population. This study aimed to investigate the effects of controlling modifiable risk factors using LS7 in MetS to prevent CVD. Methods: 44463 participants in NHANES 1999-2018 were included. The primary endpoint was a composite of CVD, including angina pectoris, coronary artery disease, myocardial infarction, congestive heart failure, and stroke. Multivariable weighted logistic regression analyses estimated the associations. The diagnosis of MetS complied with Harmonized International Diabetes Federation Criteria. Measurement of modifiable risk factors used the 2010 American Heart Association LS7 guideline and was indicated by cardiovascular health (CVH). Results: 14034 individuals were diagnosed with MetS. 4835 participants had CVD. The weighted mean CVH was 8.06 ± 0.03. Intermediate and poor CVH were associated with increased risk for CVD in participants with similar metabolic states compared to ideal CVH. By taking participants with metabolic health and ideal CVH as health control, participants with MetS and poor CVH were demonstrated to have a 3-fold (adjusted odds ratio, 4.00; 95 % confidence interval, 3.21-4.98) greater risk for CVD. Notably, under the condition of ideal CVH, the risk of having CVD was comparable between metabolic health and MetS after fully adjusted. Conclusion: Ideal control of Life's Simple 7 in metabolic syndrome contributes to a comparable risk of cardiovascular disease with healthy subjects. LS7 could be recognized as a guideline for secondary prevention in MetS.

Chronic venous disease of lower limbs in young men at high-altitude: A cross-sectional survey.

OBJECTIVES: The aim of this study was to understand the prevalence of chronic venous disease (CVD) of lower limbs in young men at high-altitude in Xizang, and to provide prevention measures. METHODS: The convenient sampling method was used to conduct a questionnaire survey among males aged 18 to 40 above an altitude of 3000 meters in Xizang in April 2023. The contents of the questionnaire included basic information, symptoms of CVD of lower limbs, protection status and training needs. Multivariate logistic regression model was calculated to evaluate the risk factors for CVD. RESULTS: A total of 350 survey questionnaires were received, and 326 valid samples were collected. The prevalence of CVD of lower limbs (C1-C6) was 37.42% (95%CI: 32.17%-42.68%), the ratio of C0 to C5 were 62.58%, 27.30%, 3.07%, 4.60%, 2.15% and 0.31%, respectively, no one reached C6. The top three symptoms of CVD were lower limb fatigue (18.10%), heaviness (15.34%) and pain (13.19%). 46.01% of respondents were unaware of CVD, and 12.88% of respondents did not have any protective measures of CVD. Multivariate logistic regression showed that age (OR = 1.076, 95%CI: 1.018-1.137, p = .009), preference for spicy food (OR = 1.747, 95%CI: 1.083-2.818, p = .022), unbalanced diet (OR = 1.877, 95%CI: 1.049-3.358, p = .034) and physical exercise (OR 0.610, 95%CI: 0.377-0.986, p = .044) were the independent risk factors for CVD. CONCLUSIONS: This study provided data on the prevalence of CVD in young men at high-altitude and the risk factors for CVD. The findings of this study may facilitate the development of individualized clinical assessments and targeted prevention programs.

Effects of different modalities of transcranial magnetic stimulation on post-stroke cognitive impairment: a network meta-analysis.

OBJECTIVE: The study aimed to evaluate, using a network meta-analysis, the effects of different transcranial magnetic stimulation (TMS) modalities on improving cognitive function after stroke. METHODS: Computer searches of the Cochrane Library, PubMed, Web of Science, Embass, Google Scholar, CNKI, and Wanfang databases were conducted to collect randomized controlled clinical studies on the use of TMS to improve cognitive function in stroke patients, published from the time of database construction to November 2023. RESULTS: A total of 29 studies and 2123 patients were included, comprising five interventions: high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS), intermittent theta rhythm stimulation (iTBS), sham stimulation (SS), and conventional rehabilitation therapy (CRT). A reticulated meta-analysis showed that the rankings of different TMS intervention modalities in terms of the Montreal Cognitive Assessment (MoCA) scores, Mini-Mental State Examination scores (MMSE), and Modified Barthel Index (MBI) scores were: HF-rTMS > LF-rTMS > iTBS > SS > CRT; the rankings of different TMS intervention modalities in terms of the event-related potential P300. amplitude scores were HF-rTMS > LF-rTMS > iTBS > CRT > SS; the rankings of different TMS intervention modalities in terms of the P300 latency scores were: iTBS > HF-rTMS > LF-rTMS > SS > CRT. Subgroup analyses of secondary outcome indicators showed that HF-rTMS significantly improved Rivermead Behavior Memory Test scores and Functional Independence Measurement-Cognitive scores. CONCLUSIONS: High-frequency TMS stimulation has a better overall effect on improving cognitive functions and activities of daily living, such as attention and memory in stroke patients.

Inhibition of GLUD1 mediated by LASP1 and SYVN1 contributes to hepatitis B virus X protein-induced hepatocarcinogenesis.

Glutamate dehydrogenase 1 (GLUD1) is implicated in oncogenesis. However, little is known about the relationship between GLUD1 and hepatocellular carcinoma (HCC). In the present study, we demonstrated that the expression levels of GLUD1 significantly decreased in tumors, which was relevant to the poor prognosis of HCC. Functionally, GLUD1 silencing enhanced the growth and migration of HCC cells. Mechanistically, the upregulation of interleukin-32 through AKT activation contributes to GLUD1 silencing-facilitated hepatocarcinogenesis. The interaction between GLUD1 and AKT, as well as α-ketoglutarate regulated by GLUD1, can suppress AKT activation. In addition, LIM and SH3 protein 1 (LASP1) interacts with GLUD1 and induces GLUD1 degradation via the ubiquitin-proteasome pathway, which relies on the E3 ubiquitin ligase synoviolin (SYVN1), whose interaction with GLUD1 is enhanced by LASP1. In hepatitis B virus (HBV)-related HCC, the HBV X protein (HBX) can suppress GLUD1 with the participation of LASP1 and SYVN1. Collectively, our data suggest that GLUD1 silencing is significantly associated with HCC development, and LASP1 and SYVN1 mediate the inhibition of GLUD1 in HCC, especially in HBV-related tumors.

Predictive values of novel high­density lipoprotein­related inflammatory indices in in­stent restenosis among patients undergoing elective percutaneous coronary intervention.

Inflammation and disorders in lipid metabolism play pivotal roles in the development and progression of in-stent restenosis (ISR). The present study aimed to investigate the association between the high-density lipoprotein (HDL)-related inflammatory indices and the risk of developing ISR among patients undergoing elective percutaneous coronary intervention (PCI). A sum of 1,471 patients undergoing elective PCI were retrospectively included and classified by tertiles of HDL-related inflammatory indices. The study endpoint was ISR. The multivariable Cox proportional hazards regression analysis with restricted cubic splines (RCS) was used to assess the associations. During a median follow-up of 62.27 months, 251 (17.06%) patients experienced ISR. The incidence of ISR increased with the increasing white blood cell-to-HDL ratio (WHR) tertiles (log-rank test, overall P=0.0082). After full adjustment, the highest tertile of WHR was significantly associated with a 1.603-fold risk of ISR (hazard ratio, 1.603; 95% confidence interval, 1.152-2.231; P=0.005) in contrast to the lowest tertile of the WHR. Results of RCS further indicated that the association between WHR and ISR was in a non-linear and dose-dependent manner (non-linear P=0.034; P overall=0.019). The lymphocyte-to-HDL ratio (LHR) and neutrophil-to-HDL ratio (NHR) were also significantly and positively associated with the risk of ISR, of which the third tertiles were at increased risk of 41.2 and 44.7% after full adjustment, respectively. Overall, lipid metabolism disorders and inflammation were interconnected in the development of ISR; therefore, HDL-related inflammatory indices, including WHR, LHR and NHR, might be potential predictors in the prognosis of elective PCI.

Angiographic microvascular resistance in patients with obstructive hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction (CMD) is an important feature of obstructive hypertrophic cardiomyopathy (oHCM). Angiographic microvascular resistance (AMR) offers a potent means for assessing CMD. This study sought to evaluate the prognostic value of CMD burden calculated by AMR among oHCM patients. METHODS: We retrospectively screened all patients diagnosed with oHCM from Fuwai Hospital between January 2017 and November 2021. Off-line AMR assessments were performed for all 3 major coronary vessels by the independent imaging core laboratory. Patients were followed every 6 months post discharge via office visit or telephone contacts. The primary outcome was major adverse cardiovascular events (MACE), including all-cause death, and unplanned rehospitalization for heart failure. RESULTS: A total of 342 patients presented with oHCM diseases enrolled in the present analyses. Mean age was 49.7, 57.6 % were men, mean 3-vessel AMR was 6.9. At a median follow-up of 18 months, high capability of 3-vessel AMR in predicting MACE was identified (AUC: 0.70) with the best cut-off value of 7.04. The primary endpoint of MACE was significantly higher in high microvascular resistance group (3-vessel AMR ≥ 7.04) as compared with low microvascular resistance group (56.5 % vs. 16.5 %; HR: 5.13; 95 % CI: 2.46-10.7; p < 0.001), which was mainly driven by the significantly higher risk of heart failure events in high microvascular resistance group. Additionally, 3-vessel AMR (HR: 4.37; 95 % CI: 1.99-9.58; p < 0.001), and age (per 1 year increase, HR: 1.03; 95 % CI: 1.01-1.06; p = 0.02) were independently associated with MACE. CONCLUSION: The present retrospective study demonstrated that the novel angiography-based AMR was a useful tool for CMD evaluation among patients with oHCM. High microvascular resistance as identified by 3-vessel AMR (≥7.04) was associated with worse prognosis.

Association of Cardiovascular Health with Cognitive Function in US Older Adults: A Population-Based Cross-Sectional Study.

INTRODUCTION: Promoting cardiovascular health (CVH) by Life's Simple 7 is associated with better cognitive function. In 2022, the American Heart Association (AHA) prompted Life's Essential 8 (LE8) to strengthen CVH assessment. This study investigated the association between the new CVH metrics assessed by LE8 and cognitive function, thus providing evidence for implementing LE8 in the primordial prevention of cognitive impairment. METHODS: 2,050 participants aged 60 and older from National Health and Nutrition Examination Survey 2011-2014 were included. Cognitive function was measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). The overall and domain-specific cognitive function z-score was created. CVH score was calculated following AHA's advisory. The multivariable linear regression model estimated the associations. RESULTS: The CVH score assessed by LE8 was independently, positively, and linearly associated with the overall cognitive function. A per-10 point increase in CVH was associated with higher overall cognitive z-scores (ß, 0.06; 95% confidence interval [CI], 0.03, 0.09), and participants with moderate (ß, -0.14; 95% CI, -0.22, -0.05) and low CVH (ß, -0.27; 95% CI, -0.37, -0.16) had lower overall cognitive z-scores compared to participants with high CVH. Similar patterns of associations were observed between CVH of AFT and DSST. Components of CVH were further associated with different domain-specific cognitive functions. CONCLUSION: Maintaining an ideal CVH improves cognitive function in older adults. Ideal adherence to individual components of LE8 was associated with improved overall and domain-specific cognitive functions. Therefore, promoting CVH according to LE8 might benefit cognitive function in the elderly.

A systematic review and meta-analysis of artificial intelligence-diagnosed endoscopic remission in ulcerative colitis.

Endoscopic remission is an important therapeutic goal in ulcerative colitis (UC). The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Mayo Endoscopic Score (MES) are the commonly used endoscopic scoring criteria. This systematic review and meta-analysis aimed to evaluate the accuracy of artificial intelligence (AI) in diagnosing endoscopic remission in UC. We also performed a meta-analysis of each of the four endoscopic remission criteria (UCEIS = 0, MES = 0, UCEIS = <1, MES = <1). Eighteen studies involving 13,687 patients were included. The combined sensitivity and specificity of AI for diagnosing endoscopic remission in UC was 87% (95% confidence interval [CI]:81-92%) and 92% (95% CI: 89-94%), respectively. The area under the curve (AUC) was 0.96 (95% CI: 0.94-0.97). The results showed that the AI model performed well regardless of which criteria were used to define endoscopic remission of UC.

Reply to Siyu Tan: Associations of cardiovascular health assessed by life's essential 8 with diabetic retinopathy and mortality in type 2 diabetes. The author's reply.

The present study is a reply of authors regarding the commentary from Siyu Tan. In this study, we paid specific attention to (1) highlight the inclusion criterion and diagnosis of Type 2 diabetes mellitus; (2) explain the assessments of cardiovascular health and diabetic retinopathy.

Hepatitis B virus core protein stabilizes RANGAP1 to upregulate KDM2A and facilitate hepatocarcinogenesis.

PURPOSE: As a vital component of the hepatitis B virus (HBV) nucleocapsid, HBV core protein (HBC) contributes to hepatocarcinogenesis. Here, we aimed to assess the effects of RANGAP1 and KDM2A on tumorigenesis induced by HBC. METHODS: Co-immunoprecipitation (Co-IP) combined with mass spectrometry were utilized to identify the proteins with the capacity to interact with HBC. The gene and protein levels of RANGAP1 and KDM2A in hepatocellular carcinoma (HCC) and HBV-positive HCC tissues were evaluated using different cohorts. The roles of RANGAP1 and KDM2A in HCC cells mediated by HBC were investigated in vitro and in vivo. Co-IP and western blot were used to estimate the interaction of HBC with RANGAP1 and KDM2A and assess RANGAP1 stabilization regulated by HBC. RESULTS: We discovered that HBC could interact with RANGAP1 and KDM2A, the levels of which were markedly elevated in HCC tissues. Relying on RANGAP1 and KDM2A, HBC facilitated HCC cell growth and migration. The increased stabilization of RANGAP1 mediated by HBC was relevant to the disruption of the interaction between RANGAP1 and an E3 ligase SYVN1. RANGAP1 interacted with KDM2A, and it further promoted KDM2A stabilization by disturbing the interaction between KDM2A and SYVN1. HBC enhanced the interaction of KDM2A with RANGAP1 and upregulated the expression of KDM2A via RANGAP1 in HCC cells. CONCLUSIONS: These findings demonstrate a novel mechanism by which HBC facilitates hepatocarcinogenesis. RANGAP1 and KDM2A could act as potential molecular targets for treating HBV-associated malignancy.

Associations of cardiovascular health assessed by life's essential 8 with diabetic retinopathy and mortality in type 2 diabetes.

BACKGROUND: Vascular complications are the leading causes of reduced life quality and mortality in type 2 diabetes mellitus (T2DM). Life's Essential 8 (LE8) is a newly modified measurement of cardiovascular health (CVH) by American Heart Association (AHA). Promoting CVH has been previously shown to improve the prognosis of T2DM. However, studies regarding the effects of CVH by LE8 on diabetic retinopathy (DR), a major microvascular complication, and death from the cardiovascular and overall causes in T2DM are currently lacking. This study aimed to investigate these associations thus providing preliminary evidence. METHODS: A total of 3192 participants from the National Health and Nutrition Examination Survey (NHANES) were included in the final analysis. Records of mortality during follow-up were obtained by linking to the National Death Index. The multivariable logistic regression and Cox proportional hazard regression with restricted cubic splines were used to estimate the associations. Subgroup analyses were performed to examine the effects of gender, age, and duration of T2DM. RESULTS: 648 individuals had DR at baseline. During a median follow-up of 76 months, 645 overall deaths (incidence per 1000 person-years, 26.53%; 95% confidence interval (CI), 26.50-26.56) were ascertained, including 216 from cardiovascular causes (incidence per 1000 person-years, 8.96%; 95% CI, 8.94-8.98). The multivariable-adjusted odds ratio (OR) per 100-point increase of LE8 was 0.80 (95% CI, 0.71-0.90) for DR, and participants with high levels of LE8 were associated with 47% risk reduction (OR, 0.53; 95% CI, 0.40-0.70). The multivariable-adjusted hazard ratio (HR) per 100-point increase of LE8 was 0.71 (95% CI, 0.62-0.81) and 0.68 (95% CI, 0.58-0.85) for all-cause mortality and cardiovascular mortality, respectively. Similar patterns of inverse associations were observed in participants with moderate and high levels of LE8 for all-cause and cardiovascular mortality. Notably, stronger associations between LE8 and mortality were discovered in participants below 60 years (P < 0.05 for interaction). Moreover, LE8 was correlated with all-cause mortality in a linear way (P for nonlinear=0.32). CONCLUSION: The AHA's newly prompted LE8 was strongly and inversely associated with the risk of DR, all-cause mortality, and cardiovascular-specific mortality in T2DM. LE8 may be a feasible and effective approach in the tertiary prevention of T2DM.

Integrating network pharmacology and experimental verification to explore the mechanisms of salidroside against myocardial fibrosis.

Myocardial fibrosis (MF) is the manifestation of a variety of cardiovascular diseases. Salidroside (SAL) has been proved to have a certain effect on anti-fibrosis in various organs. However, the mechanism of SAL in the treatment of MF remains unclear. Network pharmacology showed that there were 1228 SAL-related target genes and 2793 MF-related target genes. The intersection of these genes resulted in 271 drug-disease interactions, and 15 core active targets were filtered from protein-protein interaction mapping. The top 20 Gene ontology biological processes analysis showed that the involved processes were close to the pathogenesis of MF. Among the top 20 enriched KEGG pathways, Wnt/ß-catenin and TGF-ß1/Smad3 signaling pathways were identified. In vivo, MI rats exhibited thinning of the myocardial region and the formation of fibrous scars, the expression of smad3 and ß-catenin were increased. After SAL treatment, there was a significant reduction in collagen area and a decrease in the ratio of collagen type I to type III. The expression of smad3 and ß-catenin was suppressed and positively correlated with the dosage of SAL. SAL may contribute to the progression of MF through the TGF-ß1/Smad3 and Wnt/ß-catenin signaling pathways.

Preparation of biochar-based surface molecularly imprinted polymers and evaluation of their selective adsorption and removal of carbaryl from rice and corn.

The residue of carbaryl in food is a threat to human health. In this study, activated soybean shell biochar (A-SBC) was used as a carrier, methacrylic acid (MAA) was used as a functional monomer, and carbaryl was used as a template molecule to synthesize the activated biochar surface molecularly imprinted polymer (A-SBC@MIP). The synthesized A-SBC@MIP was characterized by SEM, FT-IR, XRD and XPS techniques, and then applied as adsorbent for carbaryl removal. The adsorption capacity of A-SBC@MIP for carbaryl was 8.6 mg‧g-1 and the imprinting factor was 1.49 at the optimum ionic strength and pH. The kinetic and isothermal data indicated that it had fast mass transfer rate and high binding capacity(Qmax=47.9 mg‧g-1). A-SBC@MIP showed good regenerative properties and the adsorption of carbaryl was excellent in its structural analogues. A solid-phase extraction (SPE) column composed of A-SBC@MIP was developed for the detection of rice and corn under optimized conditions, with recoveries of 93-101% for the spiked carbaryl. The limit of detection (LOD) of the method was 3.6 µg‧kg-1 with good linearity (R2=0.994) in the range of 0.01-5.00 mg‧L-1. The results show that the developed MIPs-SPE can enrich carbaryl from food samples as a specific and cost-effective method.

Mediation of self-concept and moderation of teacher support between SES and reading achievement: Evidence from China and the United States.

BACKGROUND: Socioeconomic status (SES) is important in students' reading development. The mechanism of how they are linked, however, is underexplored. AIMS: This research aimed to explore whether reading self-concept mediates the link between SES and reading achievement and whether teacher support moderates the direct and indirect link between SES and reading achievement. SAMPLES: Using PISA 2018 database, we selected 17,346 15-year-olds from 537 schools in B-S-J-Z (China) and the United States (U.S.). METHODS: Multilevel linear models were calculated to explore the potential mediation of self-concept and the potential moderation of teacher support between SES and reading achievement. RESULTS: Results reveal that reading self-concept mediated the link between SES and reading achievement at student level both in China and the United States, and teacher support moderated the link between SES and reading self-concept both at student level and school level only in China, but not in the United States. CONCLUSION: Our research highlights the importance of self-concept and teacher support in improving students' reading achievement, especially for students of low SES, which has important theoretical significance and practical enlightenment for reading instruction.

Insights into the impact of hepatitis B virus on hepatic stellate cell activation.

During chronic hepatitis B virus (HBV) infection, hepatic fibrosis is a serious pathological condition caused by virus-induced liver damage. The activation of hepatic stellate cells (HSCs) is a central event in the occurrence and progression of liver fibrosis. Although accumulating evidence has shown that HBV directly stimulates HSC activation, whether the virus infects and replicates in HSCs remains controversial. Inflammation is one of the obvious characteristics of chronic HBV infection, and it has been demonstrated that persistent inflammation has a predominant role in triggering and maintaining liver fibrosis. In particular, the regulation of HSC activation by HBV-related hepatocytes via various inflammatory modulators, including TGF-ß and CTGF, in a paracrine manner has been reported. In addition to these inflammation-related molecules, several inflammatory cells are essential for the progression of HBV-associated liver fibrosis. Monocytes, macrophages, Th17 cells, NK cells, as well as NKT cells, participate in the modulation of HBV-related liver fibrosis by interacting with HSCs. This review summarizes current findings on the effects of HBV and the relevant molecular mechanisms involved in HSC activation. Because HSC activation is essential for liver fibrosis, targeting HSCs is an attractive therapeutic strategy to prevent and reverse hepatic fibrosis induced by HBV infection. Video abstract.

Triglyceride-glucose index for predicting repeat revascularization and in-stent restenosis in patients with chronic coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: The triglyceride-glucose (TyG) index, a reliable surrogate indicator of insulin resistance, is independently associated with coronary artery disease of various clinical manifestations. This study aimed to investigate the prognostic value of the TyG index in predicting repeat revascularization and in-stent restenosis (ISR) in chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI). METHODS: A total of 1414 participants were enrolled and divided into groups according to the tertiles of the TyG index. The primary endpoint was a composite of PCI complications, including repeat revascularization and ISR. The associations between the TyG index and the primary endpoint were assessed by multivariable Cox proportional hazards regression analysis with restricted cubic splines (RCS). The TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). RESULTS: Over a median follow-up of 60 months, 548 (38.76%) patients had experienced at least one primary endpoint event. The follow-up incidence of the primary endpoint increased with the TyG index tertiles. After adjusting for potential confounders, the TyG index was independently associated with the primary endpoint in CCS patients (HR, 1.191; 95% CI 1.038-1.367; P = 0.013). Additionally, the highest tertile of the TyG group was correlated with a 1.319-fold risk of the primary endpoint compared with the lowest tertile of the TyG group (HR, 1.319; 95% CI 1.063-1.637; P = 0.012). Furthermore, a linear and dose-response relationship was observed between the TyG index and the primary endpoint (non-linear P = 0.373, P overall = 0.035). CONCLUSIONS: An increased TyG index was associated with elevated risk for long-term PCI complications, including repeat revascularization and ISR. Our study suggested that the TyG index could be a potent predictor in evaluating the prognosis of CCS patients undergoing PCI.

Multi-view feature representation and fusion for drug-drug interactions prediction.

BACKGROUND: Drug-drug interactions (DDIs) prediction is vital for pharmacology and clinical application to avoid adverse drug reactions on patients. It is challenging because DDIs are related to multiple factors, such as genes, drug molecular structure, diseases, biological processes, side effects, etc. It is a crucial technology for Knowledge graph to present multi-relation among entities. Recently some existing graph-based computation models have been proposed for DDIs prediction and get good performance. However, there are still some challenges in the knowledge graph representation, which can extract rich latent features from drug knowledge graph (KG). RESULTS: In this work, we propose a novel multi-view feature representation and fusion (MuFRF) architecture to realize DDIs prediction. It consists of two views of feature representation and a multi-level latent feature fusion. For the feature representation from the graph view and KG view, we use graph isomorphism network to map drug molecular structures and use RotatE to implement the vector representation on bio-medical knowledge graph, respectively. We design concatenate-level and scalar-level strategies in the multi-level latent feature fusion to capture latent features from drug molecular structure information and semantic features from bio-medical KG. And the multi-head attention mechanism achieves the optimization of features on binary and multi-class classification tasks. We evaluate our proposed method based on two open datasets in the experiments. Experiments indicate that MuFRF outperforms the classic and state-of-the-art models. CONCLUSIONS: Our proposed model can fully exploit and integrate the latent feature from the drug molecular structure graph (graph view) and rich bio-medical knowledge graph (KG view). We find that a multi-view feature representation and fusion model can accurately predict DDIs. It may contribute to providing with some guidance for research and validation for discovering novel DDIs.

Quantitation of 5α-androstanedione in normal women and women with PCOS.

In vitro studies show that 5α-androstane-3,17-dione (5α-A) is an important intermediate in the formation of dihydrotestosterone (DHT) from androstenedione (A) in women and men. Many studies involving hyperandrogenism, hirsutism, and polycystic ovary syndrome (PCOS) have measured A, testosterone (T), and DHT, but not 5α-A due to lack of a readily available assay to quantify this androgen. We have developed a specific and sensitive radioimmunoassay to measure 5α-A levels, together with A, T, and DHT, in both serum and genital skin. The present study involves 2 cohorts. Cohort 1 included 23 mostly postmenopausal women who provided both serum and genital skin to measure those androgens. In cohort 2, serum androgen levels were compared between women with PCOS and non-PCOS controls. Tissue-to-serum ratios were significantly higher for 5α-A and DHT as compared to A and T. None of the androgens showed a significant correlation between serum and genital tissue. In serum, 5α-A was significantly correlated with A, T, and DHT. In cohort 2, A, T, and DHT were significantly higher in the PCOS group compared to the control group. In contrast, 5α-A levels were similar between the 2 groups. Our findings support the view that 5α-A is an important intermediate in DHT formation in genital skin. Also, the relatively low levels of 5α-A in PCOS women suggest that it may play a more important intermediate role in the conversion of A to androsterone glucuronide.

Hepatitis B virus X protein promotes MAN1B1 expression by enhancing stability of GRP78 via TRIM25 to facilitate hepatocarcinogenesis.

BACKGROUND: GRP78 has been implicated in hepatocarcinogenesis. However, the clinical relevance, biological functions and related regulatory mechanisms of GRP78 in hepatitis B virus (HBV)-associated hepatoma carcinoma (HCC) remain elusive. METHODS: The association between GRP78 expression and HBV-related HCC was investigated. The effects of HBV X protein (HBX) on GRP78 and MAN1B1 expression, biological functions of GRP78 and MAN1B1 in HBX-mediated HCC cells and mechanisms related to TRIM25 on GRP78 upregulation to induce MAN1B1 expression in HBX-related HCC cells were examined. RESULTS: GRP78 expression was correlated with poor prognosis in HBV-positive HCC. HBX increased MAN1B1 protein expression depending on GRP78, and HBX enhanced the levels of MAN1B1 to promote proliferation, migration and PI3-K/mTOR signalling pathway activation in HCC cells. GRP78 activates Smad4 via its interaction with Smad4 to increase MAN1B1 expression in HBX-expressing HCC cells. TRIM25 enhanced the stability of GRP78 by inhibiting its ubiquitination. HBX binds to GRP78 and TRIM25 and accelerates their interaction of GRP78 and TRIM25, leading to an increase in GRP78 expression. CONCLUSIONS: HBX enhances the stability of GRP78 through TRIM25 to increase the expression of MAN1B1 to facilitate tumorigenesis, and we provide new insights into the molecular mechanisms underlying HBV-induced malignancy.

The telehealth program of occupational therapy among older people: an up-to-date scoping review.

BACKGROUND: The average life expectancy of older people is increasing, and most seniors desire to age at home and are capable of living independently. Occupational therapy (OT) is client-centered and uses patients' meaningful activities, or occupations, as treatment methods, thus playing an important role in later adulthood. Telemedicine removes the constraints of time and space, and the combination of OT and telemedicine can greatly improve medical efficiency and clinical effectiveness. AIMS: The purpose of this scoping review was to examine the scope and effectiveness of telehealth OT for older people. METHODS: This scoping review was conducted following the methodological framework proposed by Arksey and O'Malley. We searched the literature in five databases following the PICOS (Population, Intervention, Comparison, Outcome, Study design) guideline, from inception to April 2022. Two trained reviewers independently retrieved, screened, and extracted data, and used a descriptive synthesizing approach to summarize the results. RESULTS: The initial search yielded 1249 studies from databases and manual searches, of which 20 were eligible and were included in the final review. A thematic analysis revealed five main themes related to telehealth OT: occupational assessment, occupational intervention, rehabilitation counseling, caregiver support, and activity monitoring. CONCLUSIONS: Telehealth OT has been used widely for older people, focusing primarily on occupational assessment and intervention provided conveniently for occupational therapists and older clients. In addition, telehealth OT can monitor patients' activities and provide rehabilitation counseling and health education for the elderly and their caregivers, thus improving the security of their home life and the efficacy of OT. During the COVID-19 pandemic, telehealth will be an effective alternative to face-to-face modalities.