Association between hypertension and pressure ulcer: A systematic review and meta-analysis.

This review aims to systematically evaluate the association between hypertension and pressure ulcer (PU). PubMed, Embase, Web of Science, and Cochrane Library were searched for studies from their inception until September 12, 2023. Literature search, data extraction, and quality assessment were conducted independently by two researchers. The random-effects model was used to calculate the combined odds ratio (OR) and corresponding 95% confidence interval (CI) of hypertension in patients with PU; subgroup analyses were performed to explore the source of between-study heterogeneity; sensitivity analysis was used to test the robust of the combined result; and funnel plot and Egger's test were used to assess the publication bias. Finally, a total of 19 studies with 564 716 subjects were included; the overall pooled result showed no significant association between hypertension and risk of developing PU (OR = 1.15, 95% CI = 0.90-1.47, p = 0.27); and the sensitivity analysis and publication bias analysis showed robust of the combined result. Subgroup analysis indicated a significant association between hypertension and PU when the primary disease was COVID-19 (OR = 1.73, 95% CI = 1.35-2.22, p < 0.0001). No association between hypertension and PU was seen in subgroup analysis on the patient source and study design. In sum, there is no significantly statistical association between hypertension and the occurrence of PU in most cases, while the risk of PU significantly elevates among COVID-19 patients combined with hypertension regardless of patient source and study design.

HNF4α ubiquitination mediated by Peli1 impairs FAO and accelerates pressure overload-induced myocardial hypertrophy.

Impaired fatty acid oxidation (FAO) is a prominent feature of metabolic remodeling observed in pathological myocardial hypertrophy. Hepatocyte nuclear factor 4alpha (HNF4α) is closely associated with FAO in both cellular processes and disease conditions. Pellino 1 (Peli1), an E3 ligase containing a RING-like domain, plays a crucial role in catalyzing polyubiquitination of various substrates. In this study, we aimed to investigate the involvement of HNF4α and its ubiquitination, facilitated by Peli1, in FAO during pressure overload-induced cardiac hypertrophy. Peli1 systemic knockout mice (Peli1KO) display improved myocardial hypertrophy and cardiac function following transverse aortic constriction (TAC). RNA-seq analysis revealed that changes in gene expression related to lipid metabolism caused by TAC were reversed in Peli1KO mice. Importantly, both HNF4α and its downstream genes involved in FAO showed a significant increase in Peli1KO mice. We further used the antagonist BI6015 to inhibit HNF4α and delivered rAAV9-HNF4α to elevate myocardial HNF4α level, and confirmed that HNF4α inhibits the development of cardiac hypertrophy after TAC and is essential for the enhancement of FAO mediated by Peli1 knockout. In vitro experiments using BODIPY incorporation and FAO stress assay demonstrated that HNF4α enhances FAO in cardiomyocytes stimulated with angiotension II (Ang II), while Peli1 suppresses the effect of HNF4α. Mechanistically, immunoprecipitation and mass spectrometry analyses confirmed that Peli1 binds to HNF4α via its RING-like domain and promotes HNF4α ubiquitination at residues K307 and K309. These findings shed light on the underlying mechanisms contributing to impaired FAO and offer valuable insights into a promising therapeutic strategy for addressing pathological cardiac hypertrophy.

Single-cell RNA sequencing analysis revealed malignant ductal cell heterogeneity and prognosis signatures in pancreatic cancer.

Pancreatic cancer (PAC) remains one of the most lethal malignant neoplasms, which is diagnosed at an advanced stage and thus lose the chance for curative resection. Here, we further probed PAC with a comprehensive multi-omics approach. Using single-cell RNA sequencing, we provided an integrated analysis of ductal cell subpopulations over the Leiden algorithm to identify two mian subcluster: S100A6 + cells and FXYD2 + cells. The gene set enrichment analysis results show that the two subtypes focused on different pathways related to tumor development. Furthermore, we integrated bulk and single-cell RNA sequencing datasets to generate and validate the prognostic signatures of the overall survival (OS) in PAC patients and S100A6 + cells were significantly enriched in high-risk groups which had a poor prognosis. Collectively, this research expands our understanding of ductal cell and provides a new reliable prognosis signature in PAC.

Energy-Efficient Data Transmission for Underwater Wireless Sensor Networks: A Novel Hierarchical Underwater Wireless Sensor Transmission Framework.

The complexity of the underwater environment enables significant energy consumption of sensor nodes for communication with base stations in underwater wireless sensor networks (UWSNs), and the energy consumption of nodes in different water depths is unbalanced. How to improve the energy efficiency of sensor nodes and meanwhile balance the energy consumption of nodes in different water depths in UWSNs are thus urgent concerns. Therefore, in this paper, we first propose a novel hierarchical underwater wireless sensor transmission (HUWST) framework. We then propose a game-based, energy-efficient underwater communication mechanism in the presented HUWST. It improves the energy efficiency of the underwater sensors personalized according to the various water depth layers of sensor locations. In particular, we integrate the economic game theory in our mechanism to trade off variations in communication energy consumption due to sensors in different water depth layers. Mathematically, the optimal mechanism is formulated as a complex nonlinear integer programming (NIP) problem. A new energy-efficient distributed data transmission mode decision algorithm (E-DDTMD) based on the alternating direction method of multipliers (ADMM) is thus further proposed to tackle this sophisticated NIP problem. The systematic simulation results demonstrate the effectiveness of our mechanism in improving the energy efficiency of UWSNs. Moreover, our presented E-DDTMD algorithm achieves significantly superior performance to the baseline schemes.

The mechanism and efficacy of GLP-1 receptor agonists in the treatment of Alzheimer's disease.

Since type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease (AD) and both have the same pathogenesis (e.g., insulin resistance), drugs used to treat T2DM have been gradually found to reduce the progression of AD in AD models. Of these drugs, glucagon-like peptide 1 receptor (GLP-1R) agonists are more effective and have fewer side effects. GLP-1R agonists have reducing neuroinflammation and oxidative stress, neurotrophic effects, decreasing Aß deposition and tau hyperphosphorylation in AD models, which may be a potential drug for the treatment of AD. However, this needs to be verified by further clinical trials. This study aims to summarize the current information on the mechanisms and effects of GLP-1R agonists in AD.

Mendelian randomization analysis of the causal association of bone mineral density and fracture with multiple sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disorder and an autoimmune disease. Until now, observational studies have indicated the association of bone mineral density (BMD) and fracture with the risk of MS. However, these studies indicated inconsistent findings. Until now, genome-wide association studies (GWAS) have been conducted in BMD, fracture, and MS, which provide large-scale datasets to investigate the causal association of BMD and fracture with the risk of MS using the Mendelian randomization (MR) study. Here, we performed an MR study to clarify the causal association between BMD/fracture and the risk of MS using large-scale publicly available GWAS datasets from BMD, fracture, and MS. We first evaluated the bidirectional causal effects of BMD and MS. The main analysis method inverse-variance weighted (IVW) showed no significant causal effect of BMD on the risk of MS (ß = 0.058, and p = 1.98E-01), and MS on the risk of BMD (ß = -0.001, and p = 7.83E-01). We then evaluated the bidirectional causal effects of fracture and MS. However, we only identified a significant causal effect of fracture on the risk of MS using IVW (ß = -0.375, p = 0.002), but no significant causal effect of MS on the risk of the fracture using IVW (ß = 0.011, p = 2.39E-01). Therefore, our main analysis method IVW only found a significant causal effect of fracture on MS using the threshold for the statistically significant association p < 0.05/4 = 0.0125. Meanwhile, multivariable MR analyses showed that the causal effect of fracture on MS was independent of smoking, drinking, and obesity, but dependent on BMD. In summary, our MR analysis demonstrates that genetically increased fracture may reduce the risk of MS. Our findings should be further verified and the underlying mechanisms should be further evaluated by future studies.

Study on the Effect of Huanglian Jiedu Decoction on the Composition of Gut Microflora in SD Rats Based on 16S rRNA Sequencing.

OBJECTIVE: To study the effects of Huanglian Jiedu Decoction (HJD) on gut microflora of SD rats. METHOD: After 3 days of adaptive feeding, 36 rats were randomly divided into 4 groups, namely, the normal control group (NC, 10 mL/kg, distilled water), high_HJD dose group (H_HJD, 6.25 g/kg, weight ratio between crude drug and rat), medium_HJD dose group (M_HJD, 3.125 g/kg), and low_HJD dose group (L_HJD, 1.56 g/kg), and each group consisted of 9 mice. The HJD groups were then treated with orally administered HJD for 21 days, while the NC group was treated with distilled water. After 7 days, 14 days, and 21 days of the experiment and after 12 hours of fasting and water deprivation, 3 SD rats in each group were randomly sacrificed by cervical dislocation and sterile operation to collect stool faces. Sample DNA was extracted by Fecal total DNA extraction kit, sequenced using Illumina MiSeq platform, and analyzed. RESULTS: The abundance of Romboutsia, Turicibacter, Lactobacillus, and Gemella decreased, while that of Escherichia_Shigella, Coprobacillus, Blautia, Akkermansia, Klebsiella, Rhodococcus, Parabacteroides, Citrobacter, Enterococcus, Bacteroides, and Erysipelotrichaceae_incertae_sedis increased after using H_HJD. The abundance of Gemella, Turicibacter, Romboutsia, and Lactobacillus decreased, while that of Blautia, Akkermansia, Escherichia_Shigella, Thiobacillus, Rothia, Enterococcus, Lactobacillus, and Erysipelotrichaceae-incertae-sedis increased after using M_HJD. The abundance of Romboutsia, Turicibacter, Lactobacillus, and Gemella decreased, while that of Escherichia_Shigella, Bacteroides, Akkermansia, Enterococcus, Rhodococcus, Parabacteroides, Desulfovibrio, Blautia, Fusobacterium, Rothia, and Streptococcus increased after using L_HJD. CONCLUSION: HJD can regulate gut microbiota, and its effect varies with different dosage and duration of medication.

BRCA1 protects cardiac microvascular endothelial cells against irradiation by regulating p21-mediated cell cycle arrest.

AIMS: Microvascular endothelial cell dysfunction is a leading cause of radiation-induced heart disease (RIHD). BRCA1 plays an important role in DNA damage repair. The study aims to explore the effect of BRCA1 in endothelial cells involved in RIHD. MATERIALS AND METHODS: BRCA1 and p21 expression were detected in human umbilical vein endothelial cells (HUVECs) and in mouse heart tissue after irradiation exposure. The effects of BRCA1 on cell proliferation, cell cycle and radiosensitivity were determined in HUVECs with overexpression and knockdown of BRCA1. A mouse model of RIHD was established. Heart damage was detected in C57BL/6J mice and endothelial cell specific knockout BRCA1 mice (EC-BRCA1-/-). KEY FINDINGS: BRCA1 and p21 expression was significantly increased both in vitro and vivo response to irradiation. BRCA1 overexpression in endothelial cells enhanced cell growth and G1/S phase arrest, and the opposite results were observed in BRCA1 knockdown endothelial cells. BRCA1 downregulated endothelial cell cycle-related genes cyclin A, cyclin D1, cyclin E and p-Rb through increasing p21 expression, and HUVECs with BRCA1 gene knockdown were more sensitive to radiation. In vivo, a decrease in cardiac microvascular density, as well as cardiomyocyte hypoxia and apoptosis were observed in a time-dependent manner. EC-BRCA1-/- mice were more prone to severe RIHD than EC-BRCA1+/- mice after 16Gy radiation exposure due to endothelial dysfunction caused by loss of BRCA1, and p21 was declined in EC-BRCA1-/- mice heart. SIGNIFICANCE: These findings indicate that BRCA1 plays a protective role in RIHD by regulating endothelial cell cycle arrest mediated by p21 signal.

Positive association between heart dosimetry parameters and a novel cardiac biomarker, solubleST-2, in thoracic cancer chest radiation.

BACKGROUND: Early screening and diagnosis of radiation-induced heart disease (RIHD) is difficult in patients with chest radiation exposure. sST-2 is involved in myocardial stress or injury. We evaluated the relationship between heart dose parameters and sST-2 changes in chest malignant tumor patients who received chest radiation. METHODS: We prospectively collected thoracic malignancy cancer patients who had received chest radiotherapy. Heart dosimetry parameters were extracted from the treatment planning system. sST-2 was measured at baseline, the middle stage, and after radiotherapy (recorded as pre-ST-2, mid-ST-2, and post-ST-2). sST-2 change rate was calculated. Scatter plots showed the relationship between cardiac dose parameters and ST-2 change rate. Multiple regression was used to analyze the relationship between cardiac dose parameters and ST-2 change rate. RESULTS: Totally, 60 patients were enrolled. The mean V5 , V10 , V20 , V30 , V40 , and MHD was 60.93 ± 27.79%, 51.43 ± 25.44%, 39.17 ± 21.75%, 28.07 ± 17.15%,18.66 ± 12.18%, and 18.60 ± 8.63 Gy, respectively. The median M-LAD was 11.31 (IQR 3.33-18.76) Gy. The mean pre-ST-2, mid-ST-2, and post-ST-2 was 5.1 ± 3.8, 6.4 ± 3.9, and 7.6 ± 4.4, respectively. sST-2 was elevated with thoracic irradiation (P < .001). Multivariate linear regression analyses showed that V5 , V10 , V20 , and MHD were independently and positively associated with ST-2 change rate (ß = .04, .04, .04, and .10, respectively, all P < .05). CONCLUSION: Serum sST-2 levels were elevated over time during radiotherapy. V5 , V10 , V20 and MHD were independently and positively associated with the elevated ST-2 change rate.