Refining the relationship between gut microbiota and common hematologic malignancies: insights from a bidirectional Mendelian randomization study.

Background: The relationship between gut microbiota and hematologic malignancies has attracted considerable attention. As research progresses, it has become increasingly clear that the composition of gut microbiota may influence the onset and progression of hematologic malignancies. However, our understanding of this association remains limited. Methods: In our study, we classified gut microbiota into five groups based on information at the phylum, class, order, family, and genus levels. Subsequently, we obtained data related to common hematologic malignancies from the IEU Open GWAS project. We then employed a bidirectional Mendelian Randomization (MR) approach to determine whether there is a causal relationship between gut microbiota and hematologic malignancies. Additionally, we conducted bidirectional MR analyses to ascertain the directionality of this causal relationship. Results: Through forward and reverse MR analyses, we found the risk of lymphoid leukemia was significantly associated with the abundance of phylum Cyanobacteria, order Methanobacteriales, class Methanobacteria, family Peptococcaceae, family Methanobacteriaceae, and genera Lachnospiraceae UCG010, Methanobrevibacter, Eubacterium brachy group, and Butyrivibrio. The risk of myeloid leukemia was significantly associated with the abundance of phylum Actinobacteria, phylum Firmicutes, order Bifidobacteriales, order Clostridiales, class Actinobacteria, class Gammaproteobacteria, class Clostridia, family Bifidobacteriaceae, and genera Fusicatenibacter, Eubacterium hallii group, Blautia, Collinsella, Ruminococcus gauvreauii group, and Bifidobacterium. The risk of Hodgkin lymphoma was significantly associated with the abundance of family Clostridiales vadinBB60 group, genus Peptococcus, and genus Ruminococcaceae UCG010. The risk of malignant plasma cell tumor was significantly associated with the abundance of genera Romboutsia and Eubacterium rectale group. The risk of diffuse large B-cell lymphoma was significantly associated with the abundance of genera Erysipelatoclostridium and Eubacterium coprostanoligenes group. The risk of mature T/NK cell lymphomas was significantly associated with the abundance of phylum Verrucomicrobia, genus Ruminococcaceae UCG013, genus Lachnoclostridium, and genus Eubacterium rectale group. Lastly, the risk of myeloproliferative neoplasms was significantly associated with the abundance of genus Coprococcus 3 and Eubacterium hallii group. Conclusion: Our study provided new evidence for the causal relationship between gut microbiota and hematologic malignancies, offering novel insights and approaches for the prevention and treatment of these tumors.

Bilateral Pectoralis Major Muscle Flaps in Treating Deep Sternal Wound Infection following CABG in Diabetic Patients: Two Case Reports.

Deep sternal wound infection (DSWI) is a life-threatening complication after cardiac operations, especially after coronary artery bypass grafting (CABG) in diabetic patients. Bilateral pectoralis major muscle flaps have been performed to treat DSWI. Two diabetic patients suffering from DSWI after CABG were treated by bilateral pectoralis major muscle flaps in our hospital. Both patients were discharged with full recovery. Satisfactory results can be obtained with bilateral pectoralis major muscle flaps following tissue debridement and drainage. This procedure should be performed when DSWI occurs in diabetic patients after CABG.

Guar gum series affect nanostructured lipid carriers via electrostatic assembly or steric hindrance: Improving their oral delivery for phytosterols.

Surface modification of nanostructured lipid carriers (NLCs) can be an effective way to improve their oral delivery for active ingredients. In this study, four type of guar gum series modified NLCs for the delivery of phytosterols (PS) were constructed and the effects of the polysaccharides on their structure and physicochemical properties were studied. DLS and AFM results revealed that positively charged polysaccharides could bind to PS-NLCs through electrostatic attraction and made the complexes finally take positive charges, while negatively charged polysaccharides were more likely to fill in the gaps of NLC systems to achieve a balance between electrostatic repulsion and intermolecular forces. Although all four polysaccharides exhibited good storage stability and controlled release of PS in simulated intestinal digestion, PS-NLCs modified with partially hydrolyzed cationic guar gum (PHCG) at medium or high concentrations exhibited better gastric stability, mucoadhesion, and cellular uptake, which had considerable significance for improving the oral bioavailability of PS. This might be related to the coating structure of PHCG-PS-NLCs confirmed by AFM, FTIR, and Raman characterization. This study provide a reference value for designing suitable PS-NLC complexes without synthetic surfactants.

Effects of food formulation on bioavailability of phytosterols: phytosterol structures, delivery carriers, and food matrices.

Daily intake of phytosterols (PSs) as a diet supplement can lower blood-cholesterol levels and reduce the risks of cardiovascular diseases. However, the high crystallinity, low water solubility, easy oxidizability, and other characteristics of PSs restrict their application and bioavailability in food products. The formulation parameters including the structures of PSs, delivery carriers, and food matrices may play an important role in the release, dissolution, transport, and absorption of PSs in functional foods. In this paper, the effects of formulation parameters, including phytosterol structures, delivery carriers, and food matrices, on the bioavailability of phytosterols are summarized and suggestions are provided for the formulation design of functional foods. The side chain and hydroxyl esterification group of PSs may significantly affect their lipid or water solubilities and micellization capacities, which in turn affect the bioavailability of PSs. Selecting suitable delivery carriers based on the characteristics of the food system can reduce the crystallinity and oxidation of PSs and control the release of PSs, thereby improving the PS stability and delivery efficiency. Moreover, the ingredients of the carriers or food products would also influence the release, solubility, transport, and absorption of PSs in the gastrointestinal tract (GIT).

Impact of molecular interactions between hydrophilic phytosterol glycosyl derivatives and bile salts on the micellar solubility of cholesterol.

Hydrophilic phytosterol glycosyl derivatives are synthetic phytosterol analogues by coupling with the glycosyl moiety to improve the water solubility and bioaccessibility of free phytosterols. The aim of this study is to clarify the molecular interaction of phytosterol glycosyl derivatives with bile salts and the consequent impact on cholesterol solubilization. Sharp nonlinear decrease in the micellar solubility of cholesterol and accompanying changes in particle size, zeta potential and microtopography of mixed micelles were observed when phytosterol glycosyl derivatives were introduced in cholesterol-loaded bile salt micelles. These results suggested that ß-sitosterol glycosyl derivatives molecules indeed participated in the formation of mixed micelles. Further, nuclear magnetic resonance showed that the structural change of mixed micelles was caused by the insertion of ß-sitosterol glycosyl derivatives via hydrogen bonds with sodium taurocholate, which resulted in the low cholesterol solubilization. Moreover, the hydrogen-bond interactions were apparently influenced by the glycosyl moiety of ß-sitosterol glycosyl derivatives. These molecular mechanisms may contribute to the development of cholesterol-absorption inhibitors.

Chemical conversions of free phytosterols during the bleaching of corn oil.

Phytosterols have health benefits; however, they are partially removed during the bleaching of corn oil. We evaluated the chemical conversion of free phytosterols (FPs) during bleaching. FP degradation accelerated with increased time and temperature, following a first-order kinetic model. In the n-heptane system, air and activated clay promoted the chemical conversion of the FPs. Sterenes formation was analysed under different conditions using a zero-order kinetic model. The apparent activation energies revealed sterene formation decreasing in the following order: campesta-3,5-diene ≈ stigmasta-3,5,22-triene > stigmasta-3,5-diene. Isomers of the above were not detected, indicating that these sterenes were the only primary products of FPs. The desorption test indicated that the FP loss from corn oil was not only due to FPs being adsorbed the activated clay, but also FPs adsorbed at acidic activated sites being degraded. This study presents a vital scientific foundation for retaining FPs to develop healthier and more nutritious oils.

Global, national, and regional burden of acute myeloid leukemia among 60-89 years-old individuals: insights from a study covering the period 1990 to 2019.

Background: Our study examined the global, national, and regional trends in the incidence, mortality, and disability-adjusted life years (DALYs) associated with older people's acute myeloid leukemia (AML) over a 30 years period. AML, which predominantly affects individuals aged 60-89, is known for its severity and unfavorable prognosis. By providing insights into the growing burden of AML, our research highlights the urgent need for effective interventions and support at various levels. Methods: In this study, we analyzed older people with AML aged 60-89 using the Global Burden of Disease (GBD) database for 2019. Our goal was to assess trends and characteristics by examining the incidence rate, mortality rate, DALYs, and estimated annual percentage change (EAPC). We aimed to provide a comprehensive understanding of the disease's trajectory and development. Results: In 2019, the older age group of 60 to 89 years reported 61,559 new cases of AML, with the corresponding number of deaths being 53,620, and the estimated DALYs standing at 990,656. Over the last 30 years, the incidence rate of AML in this age bracket increased by 1.67 per 100,000 people, the mortality rate rose by 1.57 per 100,000 people, and the rate of DALYs, indicative of disease burden, climbed by 1.42 per 100,000 people. High Socio-demographic Index (SDI) regions, particularly high-income North America and Australia, had the highest incidence rates. Germany had the highest incidence rate among the 204 countries analyzed, while Monaco reported the highest mortality and DALY rates. Smoking, high body mass index, occupational exposure to benzene, and formaldehyde were identified as significant risk factors associated with mortality from older people with AML in 2019. Conclusion: Our study showed that the incidence, mortality, and DALY rates of AML in the older population were strongly correlated with the SDI, and these rates have been steadily increasing. This had become an increasingly serious global health issue, particularly in areas with a high SDI. We highlighted the urgency to focus more on this disease and called for the prompt implementation of appropriate preventive and control measures.

Synthesis, Physical Properties, and In Vitro-Simulated Gastrointestinal Digestion of Hydrophilic ß-Sitosterol Sugar Esters.

Hydrophilic ß-sitosterol sugar esters were synthesized by a two-step biocatalytic approach using ß-sitosterol vinyl adipate as an intermediate. The maximum conversion (above 90%) of ß-sitosterol vinyl adipate was achieved using the saccharides glucose, sucrose, and raffinose. The chemical structure of the synthesized esters was confirmed by various techniques. The investigation of physical properties revealed that ß-sitosterol sugar esters had enhanced water solubility (3.0-8.0 mM at 35 °C), reduced crystallinity, and high wettability. Their lyotropic liquid crystal properties were observed by polarized light microscopy. Furthermore, ß-sitosterol sugar esters could be hydrolyzed into ß-sitosterol adipate under simulated intestinal conditions at a low rate (2.83-18.14%). Most ß-sitosterol sugar esters probably entered into intestinal bile salt micelles with ester bonds intact and showed up to 10-fold higher in vitro bioaccessibility than free ß-sitosterol in non-fat systems. The excellent physical and functional characteristics of ß-sitosterol sugar esters suggested their great potential application in the food industry.

Total Arch Replacement Combined with Stented Elephant Trunk Implantation for Acute Type A Aortic Dissection in an Octogenarian Patient.

BACKGROUND: The indications and outcome of surgery for Acute type A aortic dissection (ATAAD) in elderly patients are still debated, especially when they were above 80 years old.  Case presentation: This report describes the case of an octogenarian patient with ATAAD who underwent total arch replacement (TAR) combined with stented elephant trunk (SET) implantation. CONCLUSION: Emergent surgery should be performed on the ATAAD octogenarians without serious preoperative complications. Acceptable outcomes could be received by total arch replacement combined with SET implantation.

Solid lipid nanoparticles for phytosterols delivery: The acyl chain number of the glyceride matrix affects the arrangement, stability, and release.

The lipid matrix plays a key role in solid lipid nanoparticles (SLNs) embedding active ingredients. To investigate the influence of lipid matrix structure on arrangement, release, and stability of solid lipid nanoparticles, three phytosterols formulations with different carrier glycerides [glycerol monostearate (GMS), glycerol distearate (GDS), and glycerol tristearate (GTS)] were prepared and evaluated. X-ray diffraction and differential scanning calorimetry revealed the lowest crystallinity of phytosterols in the GMS matrix, corresponding to the maximum bioaccessibility (40.2%) in vitro experiments. Sustained release and better stability were observed from GDS and GTS matrices, which could be attributed to strong molecular interactions or a core-rich structure inside the nanoparticles. Molecular dynamics simulations demonstrated that the affinity between phytosterols and glycerides decreased in the order GDS > GTS > GMS, as well as explaining the release and storage capacities of the three nanoparticles. This study would facilitate the rational design of SLNs in functional foods.

Non-coding RNAs Regulate the Pathogenesis of Aortic Dissection.

Aortic dissection (AD) is a fatal cardiovascular disease. It is caused by a rupture of the aortic intima or bleeding of the aortic wall that leads to the separation of different aortic wall layers. Patients with untreated AD have a mortality rate of 1-2% per hour after symptom onset. Therefore, effective biomarkers and therapeutic targets are needed to reduce AD-associated mortality. With the development of molecular technology, researchers have begun to explore the pathogenesis of AD at gene and protein levels, and have made some progress, but the pathogenesis of AD remains unclear. Non-coding RNAs, such as microRNAs, lncRNAs, and circRNAs, have been identified as basic regulators of gene expression and are found to play a key role in the pathogenesis of AD. Thus, providing a theoretical basis for developing these non-coding RNAs as clinical biomarkers and new therapeutic targets for AD in the future. Previous studies on the pathogenesis of AD focused on miRNAs, but recently, there have been an increasing number of studies that explore the role of lncRNAs, and circRNAs in AD. This review summarizes the existing knowledge on the roles of various non-coding RNAs in the pathogenesis of AD, discusses their potential role as clinical biomarkers and therapeutic targets, states the limitations of existing evidence, and recommends future avenues of research on the pathogenesis of AD.

Reactive Oxygen Species and Oxidative Stress in Vascular-Related Diseases.

Oxidative stress (OS) refers to the enhancement of oxidation and the decreased of related antioxidant enzymes activity under pathological conditions, resulting in relatively excess reactive oxygen species (ROS), causing cytotoxicity, which leads to tissue damage and is linked to neurodegenerative diseases, cardiovascular diseases, diabetes, cancers, and many other pathologies. As an important intracellular signaling molecule, ROS can regulate numerous physiological actions, such as vascular reactivity and neuronal function. According to several studies, the uncontrolled production of ROS is related to vascular injury. The growing evidence revealing how traditional risk factors translate into ROS and lead to vasculitis and other vascular diseases. In this review, we sought to mainly discuss the role of ROS and antioxidant mechanisms in vascular-related diseases, especially cardiovascular and common macrovascular diseases.

A prediction model for 30-day deaths of cirrhotic patients in intensive care unit hospitalization.

ABSTRACT: The aim of this study was to establish a prediction model for 30-day deaths of cirrhotic patients in intensive care unit.A case-control study involving 1840 patients was conducted in the Medical Information Mart of the Intensive Care Database III version 1.4. The logistic regression with L1 regularization was used to screen out the variables. The 30-day in-hospital death was used as the dependent variable and the selected variables were used as the independent variable to build a random forest model. The performance of the model was validated by the internal validation.The variables screened by logistic regression analysis were the age, heart rate, respiratory rate, systolic blood pressure, diastolic blood pressure, Oxygen saturation, white blood cells, platelets, red cell distribution width, glucose, blood urea nitrogen, bicarbonate, total bilirubin, hematocrit, alanine transaminase, aspartate transaminase, bilirubin, Simplified Acute Physiology Score II and Sequential Organ Failure Assessment. The areas under the curve of the random forest model based on these variables was 0.908, and the performance of this model were internally validated with an areas under the curve of 0.801. The random forest model displayed that Simplified Acute Physiology Score, Sequential Organ Failure Assessment, blood urea nitrogen, total bilirubin and bilirubin were more important predictors for the 30-day death of cirrhotic patients in intensive care unit.A prediction model for death of cirrhotic patients was developed based on a random forest analysis, providing a tool to evaluate the patients with a high risk of 30-day in-hospital deaths to help clinician make preventive intervention to decrease the mortality.

Catalyst-free synthesis of phytosterol diacid monoesters and their competitive effect on the solubilization of cholesterol in model bile mixed micelles.

Phytosterols have received an extensive attention owing to their excellent cholesterol-lowering activity and the role in cardiovascular diseases prevention. Phytosterol diacid monoesters, the important intermediates in the structural modification of free phytosterols, were usually obtained by chemical method with catalyst. The aim of this research was to provide an eco-friendly approach for the preparation of phytosterol diacid monoester and explore the possible mechanism of their hypocholesteremic effect using model bile mixed micelles. Catalyst-free synthesis of ß-sitosterol with succinic anhydride, maleic anhydride, and glutaric anhydride was investigated and optimized. The yields of three ß-sitosterol diacid monoesters all reached above 94% under optimum reaction conditions and their chemical structures were confirmed further by mass spectroscopy, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. Compared with ß-sitosterol, ß-sitosterol diacid monoesters possessed the increased thermal stability (up to an above 355.28°C) and improved solubility in binary mixed micelle system (exceeding 1.7 mM) and similar cholesterol-lowering activity (7.78%-11.05%). Moreover, ß-sitosterol diacid monoesters showed the competitive effect on solubilization of cholesterol due to their enhanced micellar incorporation capacity. Overall, the competition with cholesterol in vitro gives useful information about the cholesterol-lowering activity of phytosterol diacid monoesters, which will further expand their applications in the food industry and health. PRACTICAL APPLICATION: Modified phytosterols, phytosterol diacid monoesters, were successfully synthesized in petroleum ether without catalyst. These products enhanced the thermal stability of free phytosterols and reduced the dissolution capacity of cholesterol in model bile mixed micelles due to competitive solubilization. These results indicated that phytosterol diacid monoesters represented cholesterol-lowering potential, which might further expand the applications in the food industry and health.

Thermal degradation of stigmasterol under the deodorisation temperature exposure alone and in edible corn oil.

Phytosterols are commonly found in vegetable oils and possess health benefits for humans. While investigating the chemical conversion of stigmasterol at deodorisation temperatures, gas chromatography-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) experiments led to the identification of 5-ethyl-6-methyl-3-heptene-2-one, 3-hydoxy-steroid, 3-ketostigmasterol, and 3,7-diketostigmasterol as by-products. The identification of these compounds assisted in the interpretation of the stigmasterol oligomers characterised by high-pressure size exclusion chromatography (HPSEC). A similar analysis was conducted in stripped corn oil at the deodorisation temperatures. As such, 5-ethyl-6-methyl-3-heptene-2-one, 3-hydoxy-steroid, 3-ketostigmasterol and 3,7-diketostigmasterol were also detected in stripped corn oil, while the contents of 3-hydoxy-steroid and 5-ethyl-6-methyl-3-heptene-2-one were higher than those of 3-ketostigmasterol, as revealed by quantum chemical simulations. In addition, stripped corn oil exhibited the characteristic of preventing stigmasterol degradation below 200 °C, whereas it enhanced the chemical conversion (such as esterification and degradation) of stigmasterol at higher temperatures.

Enzymatic synthesis of hydrophilic phytosterol polyol esters and assessment of their bioaccessibility and uptake using an in vitro digestion/Caco-2 cell model.

A novel enzyme-catalyzed method was developed for the synthesis of phytosterol polyol esters from ß-sitosterol and polyols (sorbitol, mannitol and xylitol) by two-step transesterification using divinyl adipate (DVA) as a link. A high conversion (exceeding 94%) of ß-sitosterol with a vinyl group was achieved, in the presence of Candida rugosa lipase (CRL), at low temperature (35 °C) within 30 min. Subsequently, the maximum conversion of phytosterol polyol esters (>94%) was obtained using alkaline protease from Bacillus subtilis at 65 °C. Phytosterol polyol esters had enhanced thermal stability (up to an above 355 °C) and excellent water solubility (4.6-7.9 mM at 35 °C). Moreover, obvious increases in the bioaccessibility (41.5-63.6%) and intestinal uptake (5.2-6.5%) were observed using a simulated gastrointestinal digestion/Caco-2 cell model. These results highlighted the key role of hydrophilic structural modifications on physicochemical properties and absorption of phytosterols.

Application of the Type, Entry Site, and Malperfusion Classification in Treatment of Aortic Dissection.

BACKGROUND: Our goal is to investigate a new practical dissection classification system, including type of dissection, location of the tear of the primary entry, and malperfusion. METHODS: The outcome of 151 patients with aortic dissection between January 2019 and May 2020 retrospectively were analyzed. All cases were classified with the Stanford dissection classification (A and B) by adding type non-A non-B. They were then further classified by the new classification system, including location of the primary Entry (E) and Malperfusion (M). All cases were followed up for six months. RESULTS: The distribution of 151 patients was 53.0%, 27.8%, and 19.2%, respectively, in type A, B, and non-A non-B. The in-hospital mortality rate was 8.8%, 2.4%, and 3.4% in type A, B, and non-A non-B (P < 0.05) and postoperative neurological complications occurred in 33.8%, 7.1%, and 13.8% in type A, B, and non-A non-B (P < 0.05). Total arch replacement was performed in 53.8%, 4.8%, and 13.8% in type A, B, and non-A non-B. The in-hospital mortality rate was 12.0%, 10.4%, and 8.5% in type E1, E2 and E3, while it was 20.0%, 10.4%, and 8.5% in type M1, M2 and M3 (P < 0.05). CONCLUSIONS: The new practical dissection classification system is useful as a supplement to the Stanford dissection classification by regarding the extent of the disease process, aiding in decision-making about the operative indication and plan, and helping in anticipating prognosis.