Protective effect of Solanum Nigrum Linn green fruit ethanolic extract on alcoholic liver injury in mice

Alcoholic liver injury is a liver disease caused by excessive alcohol consumption,which can lead to chronic liver disease death.Solanum Nigrum Linn taste bitter,cold,has the effect of clearing heat and detoxification,promoting blood and detumescence.Solanum Nigrum Linn fruit contains a variety of antioxidant enzymes,can remove the body produced by aerobic metabolism harmful substances.In this paper,a model of alcohol-induced liver injury in C57BL/6 mice was established to evaluate the protective effect of Solanum Nigrum Linn green fruit(SNGF)ethanolic extract on alcohol-induced liver injury.H&E staining and oil red O(ORO)staining showed that hepatic lobules were clearly demarcated,vacuoles were significantly reduced and lipid droplets were reduced in SNGF ethanolic extract treatment group.Serum levels of TC,TG,LDH,TBA,AKP,ALT and AST were decreased in the SNGF ethanolic extract treatment group,and SNGF ethanolic extract could clear reactive oxygen species(ROS)in time.MDA content was signifi cantly decreased after SNGF ethanolic extract treatment,while superoxide dismutase(SOD)and GSH-Px contents were increased after SNGF ethanolic extract treatment.These results suggest that SNGF ethanolic extract has a protective effect on alcohol-induced liver injury.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Breeding of Ferment Bacteria and Control of Methanol and Higher Alcohols in Jujube Wine

Jujube wine is a health drink with local characteristics and is worth pro- moting. Jujube wine fermentation can be divided into alcoholic fermentation and mal- olactic fermentation. Yeast is the key of alcoholic fermentation while lactic acid bac- teria is the key of malolactic fermentation, and therefore the breeding of yeast and lactic acid bacteria is crucial for the quality of jujube wine. Besides, the control of methanol is a major problem in production, and the control of higher alcohol is also difficult. Thus, we summarized the research related with the breeding of yeast and lactic acid bacteria, and the control of methanol and higher alcohols, and proposed that breeding specialized yeast and lactic acid bacteria was the future research di- rection. Moreover, the production mechanism of methanol and higher alcohols was investigated, and the content of methanol and higher alcohols was effectively con- trolled on the basis of quality guarantee, providing references for the production technology of jujube wine.

Conversion of syngas to higher alcohols over Cu-Fe-Zr catalysts induced by ethanol

Ethanol induced method was applied to prepare Cu-Fe-Zr catalysts for conversion of syngas to higher alcohols. The catalytic performance of the catalysts induced by ethanol was superior to that of the catalyst prepared by the conventional precipitation method. Among various procedures for ethanol induced method, it was found that incorporation of ethanol in the precipitation process was the better. After incorporation of ethanol, the crystal size of CuO decreased and the reduction of copper species became easier. The better activity of Cu-Fe-Zr catalysts prepared by ethanol induced procedures was probably caused by the higher dispersion of Cu species.

Is the hypoxia-inducible factor-1 alpha mRNA expression activated by ethanol-induced injury, the mechanism underlying alcoholic liver disease?

BACKGROUND: Excessive alcohol consumption can result in multiple organ injury, of which alcoholic liver disease (ALD) is the most common. With economic development and improvement of living standards, the incidence of diseases caused by alcohol abuse has been increasing in China, although its pathogenesis remains obscure. The aim of this study was to investigate the role of hypoxia in chronic ALD. METHODS: Twenty-eight male Sprague-Dawley rats were randomized into a control group (n=12) with a normal history and an experimental group (n=16) fed with 10 ml/ kg of 56% (vol/vol) ethanol once per day by gastric lavage for 24 weeks. At 24 weeks, blood samples were collected and then the rats were killed. Liver samples were frozen at -80 ℃ and used for RT-PCR; other liver samples were obtained for immunohistochemical staining. RESULTS: When the period of alcohol consumption increased, the positive rate of expression of hypoxia- inducible factor-1 alpha (HIF-1α) mRNA was more significantly elevated in the liver of the alcohol group than in the control group (P≤0.05). The HIF-1α protein located in the cytoplasm was seldom expressed in the control group, but significantly in the alcohol group (P≤0.01). CONCLUSION: HIF-1α mRNA expression was activated by ethanol-induced injury in this study, suggesting that hypoxia is involved in the underlying mechanism of ALD.

Neurodevelopmental Timing of Ethanol Exposure May Contribute to Observed Heterogeneity of Behavioral Deficits in a Mouse Model of Fetal Alcohol Spectrum Disorder (FASD)

Maternal drinking during pregnancy can result in a wide spectrum of cognitive and behavioral abnormalities termed fetal alcohol spectrum disorders (FASD). The heterogeneity observed in FASD-related phenotypes can be attributed to a number of environmental and genetic factors;however, ethanol dose and timing of exposure may have significant influences. Here, we report the behavioral effects of acute, binge-like ethanol exposure at three neurodevelopmental times corresponding to the first, second, and third trimester of human development in C57BL/6J mice. Results show that developmental ethanol exposure consistently delays the development of basic motor skill reflexes and coordination as well as impairs spatial learning and memory. Observed changes in activity and anxiety-related behaviors, however, appear to be dependent on timing of alcohol exposure. The variability in behaviors between different treatment models suggests that these may be useful in evaluating the mechanisms disrupted by ethanol at specific neurodevelopmental times. The results provide further evidence that, regardless of developmental stage, the developing brain is acutely sensitive to alcohol exposure.

Using Raman Spectroscopy for Determination Methanol Quantity in Illegal Alcoholic Beverages

Illegal production of alcoholic beverages is a common problem in most countries.The consumption of these counterfeit alcoholic products in Turkey has increasingly been one of the major health concerns.In this study,a comparison between GC-MS and Raman spectroscopy techniques was made to determine the amount of methanol in BogmaRaki which is a counterfeit alcoholic beverage produced and consumed in Hatay region.Different ratios of methanol/ethanol concentrations were prepared to obtain a calibration curve.This curve was used to measure the amount of methanol in the actual product samples using both GC-MS and Raman spectroscopy techniques.Results obtained from both techniques were compared using Paired sample t-tests.The Limit of Detection and the Limit of Quantification values were determined as 0.03(%v/v) and 0.11(%v/v),respectively.Both techniques demonstrated a similar sensitivity in the determination of methanol concentration in these counterfeit products(p>0.05).Raman Spectroscopy,however,has an advantage of being easy to use,inexpensive,rapid and non-destructive analytical technique with little or no sample preparation.

Positive effect of ethanol-induced Lactococcus lactis on alcohol metabolism in mice

It is well known that exposure to environmental stresses could enhance the adaptability of bacteria and up-regulate the expression of a variety of oxidative stress-related genes and antioxidant enzymes.It is unclear whether the adaptability of microorganisms formed naturally in special environments could transfer to other organisms.The study aimed to evaluate the effects of untreated and ethanol-induced Lactococcus lactis intracellular extracts(U-IE and E-IE)on alcohol metabolism in mice.The positive effects of E-IE on alcohol metabolism in mice were revealed by the enhanced latency of loss of righting reflex(LORR),the reduced duration of LORR,the decrease of blood alcohol concentration,as well as the elevation of alcohol dehydrogenase(ADH)activities in the stomach and liver tissues.Furthermore,the potential benefits of E-IE on the liver were evaluated by biochemical parameters including the activities of serum transaminase,the levels of antioxidant enzymes,and the pathological changes of liver tissue.The present work put forward a new point that appropriate ethanol stress could enhance the intracellular ADH activity of L.lactis,and its intracellular extracts could continue to enhance alcohol metabolism in mice.

Ethanol induced mitochondria injury and permeability transition pore opening: Role of mitochondria in alcoholic liver disease

AIM: To observe changes of mitochondria and investigate the effect of ethanol on mitochondrial perme- ability transition pore (PTP), mitochondrial membrane potential (MMP, ΔΨm) and intracellular calcium concentration in hepatocytes by establishing an animal model of alcoholic liver disease (ALD). METHODS: Fourty adult male Wistar rats were randomly divided into two groups, the model group (20) was administered alcohol intragastrically plus an Oliver oil diet to establish an ALD model, and the control group (20) was given an equal amount of normal saline. The ultramicrostructural changes of mitochondria were observed under electron microscopy. Mitochondria of liver was extracted, and patency of PTP, mitochondrial membrane potential (ΔΨm), mitochondrial mass and intracellular calcium concentration of isolated hepacytes were detected by flow cytometry using rhodamine123 (Rh123), Nonyl-Acridine Orange and calcium fluorescent probe Fluo-3/AM, respectively. RESULTS: Membrane and cristae were broken or disappeared in mitochondria in different shapes under electron microscopy. Some mitochondria showed U shape or megamitochondrion. In the model group, liver mitochondria PTP was broken, and mitochondria swelled, the absorbance at 450 nm, A540 decreased (0.0136 ± 0.0025 vs 0.0321 ± 0.0013, model vs control, P < 0.01); mitochondria transmembrane potential (239.4638 ± 12.7263 vs 377.5850 ± 16.8119, P < 0.01) was lowered; mitochondrial mass (17.4350 ± 1.9880 vs 31.6738 ± 3.4930, P < 0.01); and [Ca2+]i was increased in liver cells (7.0020 ± 0.5008 vs 10.2050 ± 0.4701, P < 0.01).CONCLUSION: Chronic alcohol intake might lead to broken mitochondria PTP, decreased mitochondria membrane potential and injury, and elevated intracellular Ca2+ production. Ethanol-induced chondriosome injury may be an important mechanism of alcoholic diseases.

Individual Differences in Blood Alcohol Concentrations after Moderate Drinking Are Mainly Regulated by Gastric Emptying Rate Together with Ethanol Distribution Volume

Blood alcohol concentration (BAC) differs greatly among individuals, even when people of the same sex and age drink alcohol under the same drinking conditions. In this study, we investigated the main factors involved in the internal reg-ulation of individual differences in BAC, focusing on the alcohol dehydrogenase 1B (ADH1B) genotype, blood acetal-dehyde concentration (BAcH), amount of habitual alcohol consumption, pharmacokinetic parameters of BAC, distribution volume of ethanol (Vd), and gastric emptying rate (GER) under the same drinking conditions. Twenty healthy Japanese males aged between 40 and 59 years old and having the aldehyde dehydrogenase 2 (ALDH2) genotype of ALDH 2*1/*2 were recruited for this study. The subjects were given 0.32 g ethanol/kg body weight in the form of commercially available beer (5%, v/v). The results showed that BAC-max differed greatly among individuals with a more than two-fold variation. When the BAC-time curve was compared among ADH1B genotypes (ADH1B*1/*1, *1/*2, and *2/*2), there were no differences in BAC among the genotypes. Although BAcH, monthly alcohol consumption, elimination rate of blood ethanol (β value) and ethanol disappearance rate from the body (EDR) can affect BAC, all of them had no correlations with BAC-max. However, Vd (liter/kg), ΔPlasma glucose concentration (ΔPGC = PGC30 min ? PGC0 min) and the serum concentration of gastric inhibitory polypeptide (GIP) did correlate with BAC-max. Model 2 in multiple linear regression analysis showed the optimal model for Vd and GIP with positive correlations with BAC-max. As GIP and ΔPGC are both reflected by gastric emptying rate (GER), we concluded that the individual differences in BAC after moderate drinking are mainly regulated by GER together with Vd. These findings demonstrate that together with body water content, the gastrointestinal tract plays an important role in the regulation of individual differences in BAC, involving first pass metabolism of ethanol.

Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.

Effect of Ethanol Deprivation and Re-Exposure on the Ethanol Drinking Behaviour of the High-Alcohol-Drinker (UChB) Rats

Alcohol addiction constitutes a major health problem in the general population, it is a complex pathology characterized by the development of tolerance, physical dependence and compulsive ethanol-seeking behaviour that often manifests as a chronic relapsing syndrome. 0ne of the major concerns in the treatment of alcohol-dependent patients is the prevention of relapse during periods of abstinence. The alcohol deprivation effect (ADE) is defined as a temporary increase in the voluntary intake of ethanol when it is reinstated after a period of alcohol deprivation and has been used as an animal model of relapse-like drinking. ADE can be used to evaluate the efficacy of possible pharmacological agents to prevent relapse drinking. The current study was undertaken to examine whether the high-alcohol-drinker UChB rats would display an ADE. Rats were given either continuous or periodic concurrent access to 10, 20% (vol/vol) of ethanol across deprivation cycles. UChB rats consuming ethanol voluntarily for two months, exhibit a robust ADE after a single deprivation period of two weeks. The increased alcohol intake during the early days of re-exposure, following a withdrawal phase, is attributed to a shift in preference towards the higher concentration of ethanol that might reflect an increase in craving for alcohol. Since an ADE is also observed in UChB rats, make this line of rats selectively bred for their high voluntary ethanol consumption, a useful model for study the efficacy of pharmacological agents for the treatment of relapse of alcohol consumption.

Brucine N-oxide reduces ethanol intake and preference in alcohol-preferring Fawn-Hooded rats

OBJECTIVE The alcoholism-related social problems have burdened the public health heavily.A better therapy for alcohol dependence as a chronic brain disease is highly required and interests the scientists worldwide. Our group has focused on screening the right drug with low toxicity and a sound curative effect from traditional Chinese medicine. METHODS Alcohol-preferring Fawn-Hooded(FH/Wjd) rat was used as an animal model of alcoholism to evaluate the effects of brucine N-oxide(BNO),an alkoloid naturally existing in the seeds of Strychnos nux-vomica L,on the alcohol-drinking behaviors.Furthermore,its adverse action and toxicity were investigated. RESULTS Treatment with BNO at the doses of 30,50 and 70 mg · kg^(-1)reduced the voluntary alcohol consumption and preference dosedependently and selectively without altering their water intake,total fluid intake,food consumption,body weight as well as sucrose preference. Remarkably,70 mg·kg^(-1)of BNO did suppress the deprivationinduced elevation of alcohol ingestion. Moreover,BNO used at the same doses as above had no influence on locomotion in an open field test and could not result in the place preference effect. CONCLUSION Taken together,BNO is of some significant pharmacological profiles to inhibit symptoms of alcohol dependence with high safety,and thence may be a potential pharmacotherapy.

Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice,the metabolomics and gut microbiota investigation

Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.

Effect of silver-nanoparticles generated in poly(vinyl alcohol)membranes on ethanol dehydration via pervaporation

Pervaporation is an important membrane separation method of chemical engineering.In this work,silver-nanoparticles-poly(vinyl alcohol)nanocomposite membranes(AgNPs-PVA)are produced for the sake of improving its potentials for pervaporation of ethanol–water mixture so that the usual opposite trend between membrane selectivity and permeation can be reduced.The nanocomposite membranes are fabricated from an aqueous solution of poly(vinyl alcohol)with silver nanoparticles via the in-situ generation technique in the absence of any reducing agent.Successful generation of the nano size silver is measured by the UV–vis spectrum showing a single peak at 419 nm due to the plasmonic effect of silver nanoparticles.Our nanocomposite AgNPs-PVA membranes are characterized using scanning electron microscope(SEM),Fourier-transform infrared(FT-IR)spectroscopy,X-ray diffraction and thermogravimetric analysis(TGA).The pervaporation tests of our new AgNPs-PVA membranes show good results since at a higher temperature and higher ethanol concentration in the feed,the prepared membranes are highly permeable for the water having stable selectivity values and therefore our membranes show better performance compared to that of the other PVA-based nanocomposite membranes.

To Investigate the Effect of Using Ethanol Containing Wipes in Collecting Blood for the Measurement of Alcohol Concentration

This study was aimed to establish whether the skin preparation using ethanol-containing skin antiseptics causes ethanol contamination through blood collection. Venous blood was collected from 40 healthy volunteers according to the national guidelines for blood sampling, with four sequential procedures as follows: 1) collecting blood immediately (within 5 seconds) after cleaning the skin with an individually packaged type of ethanol-containing wipe, 2) collecting blood 1 minute after cleaning the skin with an individually packaged type of ethanol-containing wipe, 3) collecting immediately (within 5 seconds) after cleaning the skin with a traditional cleaning method (thoroughly ethanol-impregnated wipe, and 4) collecting 1 minute after cleaning the skin with a traditional cleaning method. Each sequential procedure was performed with and without the ethanol-containing wipe used for skin cleaning on the puncture site on their right and left arms at the time the needle was withdrawn, respectively. The collected specimens were subjected to the determination of ethanol by using headspace gas chromatography-mass spectrometry. In every 80 blood specimens obtained from 40 participants, ethanol was undetectable (<0.001 mg/mL). This study demonstrates that disinfection using ethanol-containing skin antiseptics is unlikely to cause ethanol contamination through blood collection regardless of skin preparation technique according to the guidelines for blood sampling. This may have implications in forensic science.

Sex Influence on the Formation of Alcohol Preference and Behavior in Rats during the Long-Term Caffeine and Ethanol Intake

Last years the intake of energy drinks (drinks containing caffeine and alcohol) both in young men and women has been increased. However the investigators do not pay attention to the analysis of gender differences. The goal of the study was the investigation of ethanol and caffeine influence on the alcohol preference formation and behavior in male and female rats under the conditions of long-term experiment. It has been found that six month intake of caffeine, ethanol and their combination has led to the increase of alcohol preference both in male and female rats. Alcohol preference was formed earlier in rats consumed combination of caffeine with ethanol, later on in rats consumed ethanol. In animals consumed caffeine the strong alcohol preference did not form up to the end of the experiment. Alcohol preference was higher in female rats consuming caffeine with ethanol and pure ethanol solution compared to male rats. .Behavioral activity significantly increased in females consumed caffeine and caffeine with ethanol, compared to animals received ethanol and controls. Similar tendency was observed in male rats. The anxiety level was significantly higher in females rats in all experimental groups compared to controls, while males did not demonstrate increased anxiety.

The multifaceted potential of the lipid transmitter oleoylethanolamide to treat alcohol-induced neuroinflammation and alcohol use disorders

Is there a need for new pharmacotherapies to treat alcohol use disorders(AUDs)?AUD is a highly prevalent condition in the world population that causes medical,psychological,personal,social and economic problems.The most severe dimension of AUDs is alcohol dependence,a condition in which individuals lose control over alcohol intake despite the negative consequences.Although some medications have been approved for this purpose,existing pharmacotherapies are not effective for all people due to the heterogeneity of AUDs.Current approved medications include:Disulfiram(Antabuse^?),which induces an aversion to drink by increasing alcohol metabolism-derived acetaldehyde;Naltrexone(ReVia^?,Vivitrol^?),a competitive opioid antagonist forμ-receptors that decreases heavy drinking and prevents relapse;Acamprosate(Campral^?),an indirect partial agonist at N-methyl-D-aspartic acid glutamate receptors and antagonist at metabotropic glutamate receptors that is used to prevent relapse in detoxified alcoholics.

Acute ethanol poisoning in a 6-year-old girl following ingestion of alcohol-based hand sanitizer at school

BACKGROUND： Alcohol-based hand sanitizers （ABHSs） have been widely used in homes, workplaces and schools to prevent the spread of infectious diseases. We report a young child unintentionally ingested ABHS at a school, resulting in intoxication. METHODS：The child was a 6-year-old girl who had been brought to the emergency department （ED） for hypothermia, altered mental status （AMS）, periods of hypoventilation, hypothermia and vomiting. Computed tomography of her head revealed nothing abnormal in intracranial pathology. Urine drug screening was negative. Alcohol level was 205 mg/dL on admission. Other abnormal values included potassium of 2.8 mEq/L, osmolality of 340 mOsm/kg and no hypoglycemia. Further investigation revealed that the patient had gone frequently to the class restroom for ingestion of unknown quantities of ABHSs during the day. The patient was admitted for one day for intravenous fluid hydration and close observation of her mental status. RESULTS：The patient was discharged from the hospital the next day without any complications. CONCLUSION： Despite the large safety margin of ABHSs, emergency physicians need to be aware of the potential risk of ingestion of a large amount of such products in children and consider it in the assessment and management of school-age children with acute AMS.

A Polyvinyl Alcohol/Acrylamide Hydrogel with Enhanced Mechanical Properties Promotes Full-Thickness Skin Defect Healing by Regulating Immunomodulation and Angiogenesis Through Paracrine Secretion

Hydrogel-based tissue-engineered skin has attracted increased attention due to its potential to restore the structural integrity and functionality of skin.However,the mechanical properties of hydrogel scaffolds and natural skin are substantially different.Here,we developed a polyvinyl alcohol(PVA)/acrylamide based interpenetrating network(IPN)hydrogel that was surface modified with polydopamine(PDA)and termed Dopa-gel.The Dopa-gel exhibited mechanical properties similar to native skin tissue and a superior ability to modulate paracrine functions.Furthermore,a tough scaffold with tensile resistance was fabricated using this hydrogel by three-dimensional printing.The results showed that the interpenetration of PVA,alginate,and polyacrylamide networks notably enhanced the mechanical properties of the hydrogel.Surface modification with PDA endowed the hydrogels with increased secretion of immunomodulatory and proangiogenic factors.In an in vivo model,Dopa-gel treatment accelerated wound closure,increased vascularization,and promoted a shift in macrophages from a proinflammatory M1 phenotype to a prohealing and anti-inflammatory M2 phenotype within the wound area.Mechanistically,the focal adhesion kinase(FAK)/extracellular signal-related kinase(ERK)signaling pathway may mediate the promotion of skin defect healing by increasing paracrine secretion via the Dopa-gel.Additionally,proangiogenic factors can be induced through Rho-associated kinase-2(ROCK-2)/vascular endothelial growth factor(VEGF)-mediated paracrine secretion under tensile stress conditions.Taken together,these findings suggest that the multifunctional Dopa-gel,which has good mechanical properties similar to those of native skin tissue and enhanced immunomodulatory and angiogenic properties,is a promising scaffold for skin tissue regeneration.