Polydopamine Nanostructure-Enhanced Water Interaction with pH-Responsive Manganese Sulfide Nanoclusters for Tumor Magnetic Resonance Contrast Enhancement and Synergistic Ferroptosis-Photothermal Therapy.

Rational structure design benefits the development of efficient nanoplatforms for tumor theranostic application. In this work, a multifunctional polydopamine (PDA)-coated manganese sulfide (MnS) nanocluster was prepared. The polyhydroxy structure of PDA enhanced the water interaction with pH-responsive MnS nanoclusters via hydrogen bonds. At pH 5.5 conditions, the spin-lattice relaxation rate of MnS nanoclusters dramatically increased from 5.76 to 19.33 mM-1·s-1 after the PDA coating, which can be beneficial for efficient tumor magnetic resonance imaging. In addition, PDA endowed MnS nanoclusters with excellent biocompatibility and good photothermal conversion efficiency, which can be used for efficient tumor photothermal therapy (PTT). Furthermore, MnS nanoclusters possess the ability to release H2S in the acidic tumor microenvironment, effectively inhibiting mitochondrial respiration and adenosine triphosphate production. As a result, the expression of heat shock protein was obviously reduced, which can reduce the resistance of tumor cells to photothermal stimulation and enhance the efficacy of PTT. The released Mn2+ also displayed efficient peroxidase and glutathione oxidase-like activity, effectively inducing tumor cell ferroptosis and apoptosis at the same time. Therefore, this nanoplatform could be a potential nanotheranostic for magnetic resonance contrast enhancement and synergistic ferroptosis-PTT of tumors.

The antioxidant, anti-inflammatory and analgesic activity effect of ethyl acetate extract from the flowers of Syringa pubescens Turcz.

ETHNOPHARMACOLOGICAL RELEVANCE: Syringa Pubescens Turcz. (SP), a member of the Oleaceae family, is a species of plant known as Syringa. Flowers, as the medicinal part, are commonly used in the treatment of hepatitis and tonsillitis. AIM OF THE STUDY: The research was the first to assess the antioxidant and anti-inflammatory potential of different parts of SP flowers (SPF) in vitro. The most promising fraction was ethyl acetate fraction of SP flower (SPFEA). The antioxidant, anti-inflammatory and analgesic activities of SPFEA were further studied, and the chemical components were identified. METHODS: HPLC was used to identify the major components in various fraction of SPF. DPPH and ABTS + radical scavenging assays as well as FRAP test and ß-carotene bleaching test were employed to assess the antioxidant potential of SPF fraction in vitro. The inhibitory effect on NO production in LPS-treated RAW264.7 cells and heat-induced protein denaturation test were used to evaluate the anti-inflammatory potential of SPF fraction. Further analysis of the biological activity of SPFEA was performed. Acute toxicity test was conducted to assess the toxicity of SPFEA. The anti-inflammatory effect was assessed by utilizing xylene induced ear edema model, carrageenan-induced foot edema model and peritonitis model in vivo. The analgesic effect of SPFEA was evaluated using hot plate test, tail immersion test, formaldehyde test as well as acetic acid-induced abdominal writhing pain experiment in vivo. In carrageenan induced foot edema model, ELISA kits were employed to measure levels of inflammation factors (NO, TNF-α, IL-6, COX-2, IL-1ß) in foot tissue as well as MDA, CAT, SOD, GSH-PX levels in liver tissue. RESULTS: HPLC results showed that there were significant differences in bioactive substances among different fractions of SPF, and SPFEA was rich in bioacitve components. Compared with other fractions of SPF, SPFEA exhibited better antioxidant and anti-inflammatory abilities. The 3000 mg/kg SPFEA group in mice had no obvious side effects. The xylene-induced ear edema model, carrageenan-induced foot edema and peritonitis models demonstrated that the SPFEA had significant anti-inflammatory effect. Moreover, inflammation factors including NO, TNF-α, IL-6, COX-2, IL-1ß were significantly reduced in SPFEA groups in foot tissue induced by carrageenan. Additionally, SPFEA effectively decreased liver tissue oxidative stress levels (MDA, SOD, GSH-PX and CAT). The bioactivities of SPFEA demonstrated a clear dose-dependent relationship. The results of the hot plate test, tail immersion test, formaldehyde test and acetic acid-induced abdominal writhing pain experiments indicated the SPFEA possessed an excellent analgesic effect, and this effect was in dose-dependent manner. CONCLUSION: The study provides a scientific foundation for understanding the pharmacological action of SPFEA. It has been indicated that SPFEA has excellent antioxidant, analgesic and anti-inflammatory effects.

Simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) by probe-type ultrasound-assisted natural deep eutectic solvents and their inhibition effects on low density lipoprotein oxidation.

The simultaneous extraction of crocin and geniposide from gardenia fruits (Gardenia jasminoides Ellis) was performed by integrating natural deep eutectic solvents (NADES) and ultrasound-assisted extraction (UAE). Among the eight kinds of NADES screened, choline chloride-1,2-propylene glycol was the most suitable extractant. The probe-type ultrasound-assisted NADES extraction system (pr-UAE-NADES) demonstrated higher extraction efficiency compared with plate-type ultrasound-assisted NADES extraction system (pl-UAE-NADES). Orthogonal experimental design and a modified multi-index synthetic weighted scoring method were adopted to optimize pr-UAE-NADES extraction process. The optimal extraction conditions that had a maximum synthetic weighted score of 29.46 were determined to be 25 °C for extraction temperature, 600 W for ultrasonic power, 20 min for extraction time, and 25% (w/w) for water content in NADES, leading to the maximum yields (7.39 ± 0.20 mg/g and 57.99 ± 0.91 mg/g, respectively) of crocin and geniposide. Thirty-three compounds including iridoids, carotenoids, phenolic acids, flavonoids, and triterpenes in the NADES extract were identified by LC-Q-TOF-MS2 coupled with a feature-based molecular networking workflow. The kinetics evaluation of the conjugated dienes generation on Cu2+-induced low density lipoprotein (LDL) oxidation via the four-parameter logistic regression model showed that crocin increased the lag time of LDL oxidation in a concentration-dependent manner (15 µg/mL, 30 µg/mL, 45 µg/mL) by 12.66%, 35.44%, and 73.42%, respectively. The quantitative determination for fluorescence properties alteration of the apolipoprotein B-100 exhibited that crocin effectively inhibited the fluorescence quenching of tryptophan residues and the modification of lysine residues caused by reactive aldehydes and malondialdehydes. The pr-UAE-NADES showed significant efficiency toward the simultaneous extraction of crocin and geniposide from gardenia fruits. And this study demonstrates the potential utility of gardenia fruits in developing anti-atherogenic functional food.

Facile Modification of Medical-Grade Silicone for Antimicrobial Effectiveness and Biocompatibility: A Potential Therapeutic Strategy against Bacterial Biofilms.

A one-step modification of biomedical silicone tubing with N,N-dimethyltetradecylamine, C14, results in a composition designated WinGard-1 (WG-1, 1.1 wt % C14). A surface-active silicon-amine phase (SAP) is proposed to account for increased wettability and increased surface charge. To understand the mechanism of antimicrobial effectiveness, several procedures were employed to detect whether C14 leaching occurred. An immersion-growth (IG) test was developed that required knowing the bacterial Minimum Inhibitory Concentrations (MICs) and Minimum Biocidal Concentrations (MBCs). The C14 MIC and MBC for Gm- uropathogenic E. coli (UPEC), commonly associated with catheter-associated urinary tract infections (CAUTI), were 10 and 20 µg/mL, respectively. After prior immersion of WG-1 silicone segments in a growth medium from 1 to 28 d, the IG test for the medium showed normal growth for UPEC over 24 h, indicating that the concentration of C14 must be less than the MIC, 10 µg/mL. GC-MS and studies of the medium inside and outside a dialysis bag containing WG-1 silicone segments supported de minimis leaching. Consequently, a 5 log UPEC reduction (99.999% kill) in 24 h using the shake flask test (ASTM E2149) cannot be due to leaching and is ascribed to contact kill. Interestingly, although the MBC was greater than 100 µg/mL for Pseudomonas aeruginosa, WG-1 silicone affected an 80% reduction via a 24 h shake flask test. For other bacteria and Candida albicans, greater than 99.9% shake flask kill may be understood by proposing increased wettability and concentration of charge illustrated in the TOC. De minimis leaching places WG-1 silicone at an advantage over conventional anti-infectives that rely on leaching of an antibiotic or heavy metals such as silver. The facile process for preparation of WG-1 silicone combined with biocidal effectiveness comprises progress toward the goals of device designation from the FDA for WG-1 and clearance.

Role of traditional Chinese medicine in ameliorating mitochondrial dysfunction via non-coding RNA signaling: Implication in the treatment of neurodegenerative diseases.

Neurodegenerative diseases (NDs) are common chronic disorders associated with progressive nervous system damage, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, among others. Mitochondria are abundant in various nervous system cells and provide a bulk supply of the adenosine triphosphate necessary for brain function, considered the center of the free-radical theory of aging. One common feature of NDs is mitochondrial dysfunction, which is involved in many physiopathological processes, including apoptosis, inflammation, oxidative stress, and calcium homeostasis. Recently, genetic studies revealed extensive links between mitochondrion impairment and dysregulation of non-coding RNAs (ncRNAs) in the pathology of NDs. Traditional Chinese medicines (TCMs) have been used for thousands of years in treating NDs. Numerous modern pharmacological studies have demonstrated the therapeutic effects of prescription, herbal medicine, bioactive ingredients, and monomer compounds of TCMs, which are important for managing the symptoms of NDs. Some highly effective TCMs exert protective effects on various key pathological features regulated by mitochondria and play a pivotal role in recovering disrupted signaling pathways. These disrupted signaling pathways are induced by abnormally-expressed ncRNAs associated with mitochondrial dysfunction, including microRNAs, long ncRNAs, and circular RNAs. In this review, we first explored the underlying ncRNA mechanisms linking mitochondrial dysfunction and neurodegeneration, demonstrating the implication of ncRNA-induced mitochondrial dysfunction in the pathogenesis of NDs. The ncRNA-induced mitochondrial dysfunctions affect mitochondrial biogenesis, dynamics, autophagy, Ca2+ homeostasis, oxidative stress, and downstream apoptosis. The review also discussed the targeting of the disease-related mitochondrial proteins in NDs and the protective effects of TCM formulas with definite composition, standardized extracts from individual TCMs, and monomeric compounds isolated from TCM. Additionally, we explored the ncRNA regulation of mitochondrial dysfunction in NDs and the effects and potential mechanisms of representative TCMs in alleviating mitochondrial pathogenesis and conferring anti-inflammatory, antioxidant, and anti-apoptotic pathways against NDs. Therefore, this review presents an overview of the role of mitochondrion-related ncRNAs and the target genes for TCM-based therapeutic interventions in NDs, providing insight into understanding the "multi-level compound-target-pathway regulatory" treatment mechanism of TCMs.

Evolution of phosphorus with the promotion of KOH in supercritical water gasification of dewatered cyanobacteria from ion perspective.

Phosphorus is a very important resource, and dewatered cyanobacteria contains a large amount of it. Basic additives, such as KOH, are often used to promote hydrogen production during supercritical water gasification (SCWG) of biomass, but their effects phosphorus transformation have rarely been investigated. In this study, SCWG of dewatered cyanobacteria with potassium salt and KOH was conducted in autoclave at 400 °C for 10 min, to investigate the effect of K+ on the transformation of phosphorus under neutral and alkaline conditions. Results showed that K+ increased the proportion of phosphorus in the solid phase from 88.4% to 90.8-98.3%. Furthermore, K+ could promote the transformation of iron-combined phosphorus to calcium-combined phosphorus and occluded phosphate. Only when the reaction environment was alkaline, the proportion of phosphorus in the solid phase was significantly reduced to a minimum of 26.1%. When the amount of OH- was sufficient, can this part of phosphorus and organic phosphorus, which was decomposed and transformed by the promotion of OH-, be transferred to the liquid products. Results from this study laid a foundation simultaneously for hydrogen production and phosphorus recovery more environmentally and high-effectively.

A Polyoxometalate-Encapsulated Metal-Organic Framework Nanoplatform for Synergistic Photothermal-Chemotherapy and Anti-Inflammation of Ovarian Cancer.

Photothermal therapy (PTT), as a noninvasive and local treatment, has emerged as a promising anti-tumor strategy with minimal damage to normal tissue under spatiotemporally controllable irradiation. However, the necrosis of cancer cells during PTT will induce an inflammatory reaction, which may motivate tumor regeneration and resistance to therapy. In this study, polyoxometalates and a chloroquine diphosphate (CQ) co-loaded metal-organic framework nanoplatform with hyaluronic acid coating was constructed for efficient ovarian cancer therapy and anti-inflammation. Our results demonstrated that this nanoplatform not only displayed considerable photothermal therapeutic capacity under 808 nm near-infrared laser, but also had an impressive anti-inflammatory capacity by scavenging reactive oxygen species in the tumor microenvironment. CQ with pH dependence was used for the deacidification of lysosomes and the inhibition of autophagy, cutting off a self-protection pathway induced by cell necrosis-autophagy, and achieving the synergistic treatment of tumors. Therefore, we combined the excellent properties of these materials to synthesize a nanoplatform and explored its therapeutic effects in various aspects. This work provides a promising novel prospect for PTT/anti-inflammation/anti-autophagy combinations for efficient ovarian cancer treatment through the fine tuning of material design.

Protective Effects of Herba Houttuyniae Aqueous Extract against OVA-Induced Airway Hyperresponsiveness and Inflammation in Asthmatic Mice.

Herba Houttuyniae is the well-knownfood-medicine herb with the special taste and smell. It is also widely used in south China for prevention of various chronic pulmonary inflammatory diseases including asthma. However, the active ingredients and therapeutic mechanism of this herb remain obscure. In this study, network pharmacology technology was employed to investigate the effects of Herba Houttuyniae aqueous extract (HHAE) on OVA-induced airway hyperresponsiveness and inflammation. The results showed that six compounds (isoramanone, kaempferol, 1-methyl-2-nonacosyl-4-quinolone, C09747, spinasterol, and quercetin) were found to be mainly responsible for the therapeutic effects of the herb, which totally regulated the expressions of 168 asthma-related proteins. All those targets involved in the signal transduction of the prolactin signaling pathway, central carbon metabolism in cancer, EGFR tyrosine kinase inhibitor resistance, endocrine resistance, and VEGF signaling pathway. The in vivo experiment also revealed that orally administrated with HHAE alleviated airway hyperresponsiveness and inflammation in OVA-induced asthmatic mice. It significantly decreased the counts of neutrophils, eosinophils, and lymphocytes as well as the levels of IL-1ß, IL-4, IL-6, and IL-13 in BALF of asthmatic mice. Mechanically, HHAE downregulated both the mRNA and protein expressions of p38 MAPK, PI3K, AKT, and VEGF in the lung tissues of asthmatic mice. Therefore, HHAE improved OVA-induced airway hyperresponsiveness and inflammation in mice and could be a potential supplement for asthma treatment.

Improvement of Ulcerative Colitis by Aspartate via RIPK Pathway Modulation and Gut Microbiota Composition in Mice.

The intestine requires a great deal of energy to maintain its health and function; thus, energy deficits in the intestinal mucosa may lead to intestinal damage. Aspartate (Asp) is an essential energy source in the intestinal mucosa and plays a vital part in gut health. In the current study, we hypothesized that dietary supplementation of Asp could alleviate DSS-induced colitis via improvement in the colonic morphology, oxidative stress, cell apoptosis, and microbiota composition in a mouse model of dextran. Asp administration decreased the disease activity index, apoptosis, myeloperoxidase, eosinophil peroxidase, and proinflammatory cytokine (IL-1ß and TNF-α) concentrations in the colonic tissue, but improved the body weight, average daily food intake, colonic morphology, and antioxidant-related gene (GPX1 and GPX4) expression in DSS-treated mice. Expression levels of RIPK1 and RIPK3 were increased in the colon following Asp administration in the DSS-induced mice, whereas the MLKL protein expression was decreased. 16S rRNA sequencing showed that Asp treatment increased the abundance of Lactobacillus and Alistipes at the gene level, and Bacteroidetes at the phylum level, but decreased the abundance of Actinobacteria and Verrucomicrobia at the phylum level. Asp may positively regulate the recovery of DSS-induced damage by improving the immunity and antioxidative capacity, regulating RIPK signaling and modulating the gut microbiota composition.

Effects of Dietary Protein Level on the Microbial Composition and Metabolomic Profile in Postweaning Piglets.

Since the human and porcine digestive systems have similar anatomical structures and physiological functions, pigs are a useful animal model for studying human digestive diseases. By investigating intestinal metabolites in piglets after weaning, this study attempted to identify the inherent connection between dietary protein levels and changes in the intestinal microbiota of piglets. Casein was employed as the only source of protein for the piglets in this study to avoid the influence of other protein sources. 14 weaning at 28-day-old piglets (6.9 ± 0.19 kg) formed into two dietary groups: 17% casein fed group (LP) and 30% casein fed group (HP). Piglets were allowed to free food and water during the 2-week experiment. Throughout the trial, the piglets' diarrhea index (1: no diarrhea and 3: watery diarrhea) and food intake were noted during the experiment. We discovered piglets fed a high-protein diet developed diarrhea throughout the duration of the research, whereas piglets fed a normal protein diet did not. In addition, the HP group had lower feed intake and body weight than the control group (P < 0.05). The HP diet influenced the content of short-chain and branched-chain fatty acids in the colon, including acetate and isovaleric acid. The ileal microbiota's 16S rRNA gene was sequenced, and it was discovered that the relative abundance of gastrointestinal bacteria differed between the HP and control groups. Dietary protein levels influenced bile acid biosynthesis, alpha-linolenic acid metabolism, phospholipid biosynthesis, arachidonic acid metabolism, fatty acid biosynthesis, retinol metabolism, arginine and proline metabolism, pyrimidine metabolism, tryptophan metabolism, and glycine and serine metabolism, according to gas chromatography-mass spectrometry analysis. Furthermore, a correlation analysis of the pooled information revealed a possible link between intestinal metabolites and specific bacteria species. These findings demonstrate that weaned piglets' microbiota composition and metabolites are modified by a high-protein diet and thus inducing severe postweaning diarrhea and inhibiting growth performance. However, the potential molecular mechanism of this regulation in the growth of piglets remains unclear.

The epidemiology, treatment patterns, healthcare utilizations and costs of Acute Myeloid Leukaemia (AML) in Taiwan.

BACKGROUNDS: An increasing incidence of Acute Myeloid Leukaemia (AML) has been reported in several Western countries. However, the epidemiology of AML in Asia is very limited. According to the National Comprehensive Cancer Network (NCCN) guideline of AML, a range of conventional therapy options is available to AML patients. Nevertheless, different treatment strategies may result in diverse healthcare utilization and costs. Understanding the treatment patterns, healthcare utilization and costs of AML would thus be essential for clinicians and policymakers to optimize the treatment strategies of AML. OBJECTIVES: The objective of this study was to investigate the incidence, treatment patterns, healthcare utilization and costs of AML in Taiwan using a nationwide population database. METHODS: We retrospectively identified AML patients diagnosed from 2006 to 2015 from the Taiwan Cancer Registry Database (TCRD) and estimated the epidemiology of AML in Taiwan. The TCRD was linked to National Health Insurance Research Database (NHIRD) to collect the treatment patterns and health care utilization. Patients diagnosed with AML from 2011 to 2015 were further identified to analyze treatment patterns, healthcare utilization and costs. RESULTS: The crude annual incidence of AML increased from 2.78 to 3.21 cases per 100,000 individuals from 2006 to 2015. However, the age-standardized rate (ASRs) of AML slightly declined from 2.47 to 2.41 cases per 100,000 individuals in the same period. Among 2,179 AML patients who received induction therapy (median age: 56 years), most of them (n = 1744; 80.04%) received standard-dose cytarabine (SDAC) regimen. The remaining 162 patients received high dose cytarabine (HDAC) and 273 patients received non-standard dose cytarabine (N-SDAC) regimen as the induction therapy. The median medical costs in our study for patients treated with chemotherapy alone was $42,271 for HDAC, $36,199 for SDAC and $36,250 for N-SDAC. For those who received hematopoietic stem cell transplantation (HSCT) after induction therapy, their median medical costs were $78,876 for HDAC, $78,593 for SDAC and $79,776 for N-SDAC. CONCLUSIONS: This study is the first population-based study conducted in Asia to provide updated and comprehensive information on epidemiology, treatment patterns and healthcare resource utilization and costs of AML.

Glutathione Protects against Paraquat-Induced Oxidative Stress by Regulating Intestinal Barrier, Antioxidant Capacity, and CAR Signaling Pathway in Weaned Piglets.

Endogenous glutathione (GSH) effectively regulates redox homeostasis in the body. This study aimed to investigate the regulatory mechanism of different dietary levels of GSH supplementation on the intestinal barrier and antioxidant function in a paraquat-induced stress-weaned piglet model. Our results showed that dietary 0.06% GSH supplementation improved the growth performance of weaned piglets under normal and stressful conditions to some degree and decreased the diarrhea rate throughout. Exogenous GSH improved paraquat-induced changes in intestinal morphology, organelle, and permeability and reduced intestinal epithelial cell apoptosis. Moreover, GSH treatment alleviated intestinal oxidative stress damage by upregulating antioxidant (GPX4, CnZnSOD, GCLC, and GCLM) and anti-inflammatory (IL-10) gene expression and downregulating inflammatory cytokines (IFN-γ and IL-12) gene expression. Furthermore, GSH significantly reduced the expression levels of constitutive androstane receptor (CAR), RXRα, HSP90, PP2Ac, CYP2B22, and CYP3A29, and increased the expression levels of GSTA1 and GSTA2 in the jejunum and ileum of paraquat-induced piglets. We conclude that exogenous GSH protects against oxidative stress damage by regulating the intestinal barrier, antioxidant capacity, and CAR signaling pathway.

Efficacy of Different Preemptive Analgesia on Postoperative Analgesia, Oxidative Stress, and Inflammatory Response after Gynecological Laparoscopic Surgery.

OBJECTIVE: To observe and compare the analgesic effects of oxycodone, pentazocine, and ketorolac tromethamine pre-emptive analgesia on gynecological laparoscopic patients after operation and the effects on oxidative stress and inflammatory reaction. METHODS: A total of 64 patients who underwent elective gynecological laparoscopic surgery in Yiwu Central Hospital from June 2019 to December 2020 were randomly divided into four groups (n = 16). Before anesthesia induction, oxycodone (group A), pentazocine (group B), ketorolac tromethamine (group C), and normal saline (group D) were, respectively, administered. Patients' mean arterial pressure (MAP) and heart rate (HR) changes, visual analogue scale (VAS), Bruggemann comfort scale (BCS), serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), blood glucose (CLU), serum cortisol level, postoperative adverse reactions, and additional analgesia were recorded at each time point. RESULTS: The MAP levels of T2 (immediate intubation), T3 (immediate catheter removal), and T4 (5 min after catheter removal) in the four groups were higher than those of T1 (quiescent state), and the HR levels T2, T3, and T4 were lower than those of T1 (P < 0.05). The MAP and HR levels of T2, T3, and T4 in patients of groups A, B, and C were lower than those of group D in the same period (P < 0.05). The VAS and BCS scores of groups A, B, and C at 1, 6, 12, and 24 h after operation were better than those of group D at the same time, and the scores of group A at 1 h and 6 h after operation were better than those of groups B and C at the same time (P < 0.05). The levels of serum TNF-α, IL-6, and CRP in the four groups of patients at 6, 12, and 24 h after operation were higher than those before operation, but those in groups A, B, and C were lower than those in group D, and those in group A were higher than those in groups B and C at 12 h and 24 h after operation (P < 0.05). The CLU and serum cortisol levels in the four groups were significantly higher at 6, 12, and 24 h after operation, but those in groups A, B, and C were lower than those in group D, and those in group A were lower than those in groups B and C at 6 and 12 h after operation (P < 0.05). There was no significant difference in the incidence of adverse reactions within 24 h between the four groups (P > 0.05). The incidence of additional analgesia in groups A, B, and C was lower than that in group D (P < 0.05). CONCLUSION: Oxycodone, pentazocine, and ketorolac tromethamine are effective and safe in inhibiting postoperative pain and the generation of inflammatory factors and relieving inflammatory state in gynecological laparoscopic pre-emptive analgesia. Oxycodone has better postoperative analgesic effect because it can effectively alleviate stress reaction.

Energy Achievement Rate Is an Independent Factor Associated with Intensive Care Unit Mortality in High-Nutritional-Risk Patients with Acute Respiratory Distress Syndrome Requiring Prolonged Prone Positioning Therapy.

Early enteral nutrition (EN) and a nutrition target >60% are recommended for patients in the intensive care unit (ICU), even for those with acute respiratory distress syndrome (ARDS). Prolonged prone positioning (PP) therapy (>48 h) is the rescue therapy of ARDS, but it may worsen the feeding status because it requires the heavy sedation and total paralysis of patients. Our previous studies demonstrated that energy achievement rate (EAR) >65% was a good prognostic factor in ICU. However, its impact on the mortality of patients with ARDS requiring prolonged PP therapy remains unclear. We retrospectively analyzed 79 patients with high nutritional risk (modified nutrition risk in the critically ill; mNUTRIC score ≥5); and identified factors associated with ICU mortality by using a Cox regression model. Through univariate analysis, mNUTRIC score, comorbid with malignancy, actual energy intake, and EAR (%) were associated with ICU mortality. By multivariate analysis, EAR (%) was a strong predictive factor of ICU mortality (HR: 0.19, 95% CI: 0.07-0.56). EAR >65% was associated with lower 14-day, 28-day, and ICU mortality after adjustment for confounding factors. We suggest early EN and increase EAR >65% may benefit patients with ARDS who required prolonged PP therapy.

Caloric Intake with High Ratio of Enteral Nutrition Associated with Lower Hospital Mortality for Patients with Acute Respiratory Distress Syndrome Using Prone Position Therapy.

Positioning patients in the prone position leads to reduced hospital mortality rates for those with severe acute respiratory distress syndrome (ARDS). What constitutes the optimal feeding strategy for prone patients with ARDS is controversial. We conducted a retrospective study that enrolled 110 prone patients with ARDS in two medical intensive care units (ICUs) from September 2015 to November 2018. Inclusion criteria were as follows: age ≥20 years, diagnosis of respiratory failure requiring mechanical ventilation, diagnosis of ARDS within 72 h of ICU admission, placement in a prone position within the first 7 days of ICU admission, and ICU stay of more than 7 days. Exclusion criteria were as follows: nil per os orders because of gastrointestinal bleeding or hemodynamic instability, and ventilator dependency because of chronic respiratory failure. The consecutive daily enteral nutrition(EN)/EN + parenteral nutrition(PN) ratio could predict hospital mortality rates within the first 7 days of admission when using generalized estimating equations (p = 0.013). A higher average EN/EN + PN ratio within the first 7 days predicted (hazard ratio: 0.97, confidence interval: 0.96-0.99) lower hospital mortality rates. To reduce hospital mortality rates, caloric intake with a higher EN ratio may be considered for patients in prone positions with ARDS.

Music and art therapy combined with cognitive behavioral therapy to treat adolescent anorexia patients.

OBJECTIVE: To investigate the efficacy and feasibility of music and art therapy combined with cognitive behavioral therapy (CBT) in the treatment of adolescent patients with anorexia. METHODS: A total of 77 patients admitted to our hospital from August 2018 to October 2019 were recruited as the study cohort, but 11 patients who dropped out of the study were excluded. The data from the 66 patients were collected for a statistical analysis. There were 31 patients in the control group and 35 patients in the treatment group. After the intervention, the body weight, cognitive and behavioral ability, emotional reaction, and treatment satisfaction changes were compared and analyzed in the two groups. RESULTS: The treatment group had a significantly lower dropout rate and higher overall treatment satisfaction than the control group. After the intervention, the body weights, body mass indexes (BMI), and abdominal subcutaneous fat thicknesses were increased in the two groups, and the increase in the treatment group was significantly higher than it was in the control group (P < 0.05). After the intervention, the Eating Disorder Examination Questionnaire 6.0 (EDE-Q-6.0), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) scores were significantly lower than they were before the intervention, and the scores in the treatment group were significantly lower than they were in the control group (P < 0.05). CONCLUSION: Music and art therapy combined with CBT can effectively improve patients' recognition and acceptance of the treatment, the therapeutic effects, and the adverse emotional reactions (e.g., depression and anxiety), and help patients establish the correct cognition regarding food, body shape, and weight.

Chronotherapy for morning blood pressure surge in hypertensive patients: a systematic review and meta-analysis.

BACKGROUND: The morning blood pressure surge (MBPS) is related to an exaggerated risk of cardiovascular diseases and mortality. With increasing attention on circadian change in blood pressure and extensive use of ambulatory blood pressure monitoring (ABPM), chronotherapy that administration of medication according to biological rhythm, is reported to improve cardiovascular outcomes. The aim of this study is to evaluate the influence of chronotherapy of antihypertensive drugs upon MBPS in hypertensive patients. METHODS: A search strategy was applied in Ovid MEDLINE, EMBASE, Cochrane (Wiley) CENTRAL Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the Chinese Biomedical literature database. No language and date restrictions. Randomized controlled trials (RCT) assessing the efficacy of evening and morning administration of the same medications in adult patients with primary hypertension were included. RESULTS: A total of ten trials, comprising 1724 participants with a mean age of 61 and 51% female, were included in this study. Combined analysis observed significant reduction of MBPS (- 5.30 mmHg, 95% CI - 8.80 to - 1.80), night-time SBP (- 2.29 mmHg, 95% CI - 4.43 to - 0.15), night-time DBP (- 1.63 mmHg, 95 %CI - 3.23 to - 0.04) and increase in night blood pressure dipping (3.23%, 95% CI 5.37 to 1.10) in evening dosage compared with traditional morning dosage of blood pressure-lowering drugs. No significant difference was found in the incidence of overall adverse effects (RR 0.65, 95% CI 0.30 to 1.41) and withdrawal due to adverse effects (RR 0.95, 95% CI 0.53 to 1.71). CONCLUSIONS: Our study suggested that evening administration of antihypertensive medications exerted better blood pressure-lowering effect on MBPS compared with conventional morning dosage. Safety assessment also indicated that the evening regimen did not increase the risk of adverse events. However, endpoint studies need to be carried out to confirm the significance and feasibility of this treatment regimen in clinical practice.

Mechanism of separation and removal of water from oily sludge using liquid dimethyl ether to dissolve hydrocarbons.

The effective disposal of oily sludge generated from the petroleum industry has received increasing concern. The primary difficulty for the reduction and resource utilization of oily sludge is dewatering. Therefore, finding an efficient and energy-saving dewatering technology is an urgent need for the treatment of oily sludge. In this study, an innovative developed method using liquefied dimethyl ether (L-DME) for dewatering is employed to deal with oily sludge for the first time. Oily sludge from a refinery was used to conduct experiments in sequencing dissolution-separation reactors. Changes in the dehydration rate, oil recovery, group components (hydrocarbon series of petroleum, including saturates, aromatics, resins and asphaltenes) at different extraction time, temperatures and L-DME additions were measured. The results revealed that L-DME removed 90% of the water and recovered 40% of the oil, which was an amazing dehydration effect for oily sludge. The water-binding form of oily sludge is different from sewage sludge and other biomass and the water in oily sludge is in a stable water-in-oil (W/O) suspension emulsified state. L-DME was mixed with semi-colloidal like oily sludge to break the structure of the water-in-oil emulsion, making the mixture into a solid-liquid two phase substances that were easy to separate, thus achieving a high degree of separation of water. The dissolution of saturated hydrocarbons, aromatic hydrocarbons, and small amounts of colloid by L-DME played an important auxiliary role in water removal.

Synthesis and biological evaluation of acridine-based histone deacetylase inhibitors as multitarget agents against Alzheimer's disease.

Multitarget agents simultaneously trigger molecules in functionally complementary pathways, and are therefore considered to have potential in effectively treating Alzheimer's disease (AD), which has a complex pathogenetic mechanism. In this study, the HDAC inhibitor core is incorporated into the acetylcholine esterase (ACE) inhibitor acridine-derived moiety and resulted in compounds that exhibited higher class IIa HDAC (4, 5, 7, and 9)- and class IIb HDAC6-inhibiting activity when compared to the pan-HDAC inhibitor SAHA in clinical practice. One of these compounds, 11b, displayed greater selectivity toward HDAC6 than other isoform enzymes. In contrast, the activity of compound 6a was selective toward class IIa HDAC and HDAC6. These two compounds exhibited strong activity against Aß-aggregation as well as significantly disrupted Aß-oligomer. Additionally, 11b and 6a strongly inhibited AChE. These experimental findings demonstrate that compounds 11b and 6a are HDAC-Aß-aggregation-AChE inhibitors. Notably, they can enhance neurite outgrowth, but with no significant neurotoxicity. Further biological evaluation revealed the various cellular effects of multitarget compounds 11b and 6a, which have the potential to treat AD.