Prognostic value of cortisol and thyroid function tests in poisoned patients admitted to toxicology ICU

BACKGROUND: Prognostic value of cortisol and thyroid function tests(TFTs) has previously been evaluated in medical ICUs. We aimed to evaluate prognostic efficacy of cortisol and TFTs in critically ill poisoned patients admitted to toxicology intensive care unit(ICU).METHODS: In a prospective study of consecutively enrolled subjects admitted to the toxicology ICU, lab analyses included TFTs(total T3 and T4 as well as TSH) and cortisol levels drawn between 8 am–10 am during period of the first 24 hours post-ingestion/exposure. Simplified Acute Physiology Score Ⅱ(SAPS Ⅱ) and Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ) were recorded. All scores were compared to detect the best prognostic factor. Type of poisoning was also included.RESULTS: In 200 patients evaluated, 129 were male and mean age was 31 years. In general, SAPS Ⅱ, T4, and cortisol could prognosticate death. After regression analysis, only cortisol had such efficacy(P=0.04; OR=1.06; 95%CI=1.05–1.08; cut-off=42 μg/d L; sensitivity=70%; specificity=82%). Between aluminium phosphide(ALP)-and non ALP-poisoned patients, level of consciousness, mean arterial pressure, and cortisol level could prognosticate death in ALP poisoning(all Ps<0.001 in both uni and multivariate analyses). Median(interquartile range; IQR) GCS was 7(6, 10) and 15(8, 15) in non-ALP and ALP-poisoned patients(P<0.003). SAPS Ⅱ and APACHE Ⅱ could not prognosticate death at all.CONCLUSION: Cortisol best prognosticated outcomes for subjects admitted to the toxicology ICU. Its level is higher in ALP-poisoned patients probably due to the higher stress while they remain conscious till the final stages of toxicity and are aware of deterioration of their clinical condition or may be due to their significantly lower blood pressures.

Calcium Glucarate Prevents Tumor Formation in Mouse Skin

Objective Calcium Glucarate (Cag), Ca salt of D-glucaric acid is a naturally occurring non-toxic compound present in fruits, vegetables and seeds of some plants, and suppress tumor growth in different models. Due to lack of knowledge about its mode of action its uses are limited in cancer chemotherapy thus the objective of the study was to study the mechanism of action of Cag on mouse skin tumorigenesis. Methods We have estimated effect of Cag on DMBA induced mouse skin tumor development following complete carcinogenesis protocol. We measured, epidermal transglutaminase activity (TG), a marker of cell differentiation after DMBA and/or Cag treatment and [3H] thymidine incorporation into DNA as a marker for cell proliferation. Results Topical application of Cag suppressed the DMBA induced mouse skin tumor development. Topical application of Cag significantly modifies the critical events of proliferation and differentiation TG activity was found to be reduced after DMBA treatment. Reduction of the TG activ

Abdominal pain related to adulterated opium:An emerging issue in drug addicts

Lead may contaminate opium,heroin and illicit opiates and is particularly observed in Iran.Lead,a natural heavy metal is able to interfere with several organ functions after ingestion or inhalation.Lead poisoning manifestations are non-specific and thus lead poisoning remains difficult to diagnose.Among the manifestations,abdominal pain is almost the most frequent symptom causing patients to seek medical care.In patients with a history of opium addiction presenting with moderate-to-severe abdominal pain,lack of diagnosis of lead toxicity may thus result in time-consuming and unnecessary medical work-ups that can end up in invasive surgery.This paper aims to briefly review abdominal pain as an emergency issue and the leading symptom of lead poisoning that brings most of the patients to healthcare facilities.All published adult cases and case series of opium addicts admitted with abdominal pain due to leadadulterated opium consumption have been reviewed.A trend of increasing numbers of lead poisoning cases has recently emerged among opium addicts in Iran.Due to the non-specific manifestations and hazardous effects,psychiatrists and emergency physicians should consider lead poisoning in patients with a past or present history of opium addiction referred for acute abdominal pain,particularly in case of colicky abdominal pain.

Severity of the metabolic syndrome as a predictor of prediabetes and type 2 diabetes in first degree relatives of type 2 diabetic patients:A 15-year prospective cohort study

BACKGROUND Type 2 diabetes mellitus(T2DM)has high morbidity and mortality worldwide,therefore there is of paramount importance to identify the risk factors in the populations at risk early in the course of illness.A strong correlation between severity of metabolic syndrome(MetS)and HbA1c,fasting insulin and insulin resistance has been reported.Accordingly,the MetS severity score(or MestS Zscore)can potentially be used to predict the risk of T2DM progression over time.AIM To evaluate the association the of MestS Z-score in first degree relatives(FDRs)of T2DM with the risk of prediabetes and type 2 diabetes in future.METHODS A prospective open cohort study was conducted between 2003-2018.At baseline,the sample comprised of 1766 FDRs of patients with T2DM who had a normal glucose tolerance test.Relative risk(RR)and 95%confidence interval were calculated based on logistic regression.The receiver-operator characteristic analysis and area under the curve based on MetS Z-score were used to evaluate the risk of prediabetes and diabetes among the FDR population.RESULTS Baseline MetS Z-scores were associated with the its latest values(P<0.0001).Compared with individuals who were T2DM free at the end of follow up,those who developed T2DM had higher MetS Z-score at baseline(P<0.001).In multivariable logistic regression analyses for every unit elevation in MetS Z-score at the baseline,the RR for developing future T2DM and prediabetes was(RR=1.94,RR=3.84),(RR=1.5,RR=2.17)in total population and female group,respectively(P<0.05).The associations remained significant after adjusting the potential confounding variables.A cut off value of 0.97 and 0.94 was defined in the receiver-operator characteristic curve based on the MetS Z-score for differentiating female patients with diabetes and prediabetes from the normal population,respectively.CONCLUSION The MetS Z-score was associated with an increased risk of future T2DM.Appropriate interventions at earlier stages for preventing and attenuating MetS effects may be considered as an effective strategy for FDR as at-risk population.

Trend of blood lactate level in acute aluminum phosphide poisoning

BACKGROUND: Aluminum phosphide(Al P) poisoning is common in the developing countries. There is no specifi c antidote for the treatment of acute Al P poisoning. Early diagnosis of poisoning and outcome predictors may facilitate treatment decisions. The objective of this study was to determine the trend of blood lactate level in acute Al P poisoning to evaluate its role as a prognostic factor.METHODS: This was a prospective study on acute Al P intoxicated patients during one year. Demographic data, clinical and laboratory data on admission, and outcome were recorded in a selfmade questionnaire. Blood lactate levels were analyzed every two hours for 24 hours.RESULTS: Thirty-nine(27 male, 12 female) patients were included in the study. The mortality rate was 38.5%. The mean blood pressure, pulse rate, blood p H and serum bicarbonate level were significantly different between the survivors and non-survivors groups. Blood lactate level was signifi cantly higher in the non-survivors group during 8 to 16 hours post ingestion.CONCLUSION: Blood lactate level could be used as an index of severity of acute Al P poisoning.

Effect of sample treatment on determination of arsenic （Ⅲ） and arsenic （Ⅴ） in aqueous and tissue samples by hydride generation atomic absorption spectrometry

The purpose of this procedure was to optimize and improve a method that used for the determination of arsenic （Ⅲ） and arsenic （Ⅴ） in biological and environmental samples. The method is based on hydride generation and atomic absorption spectrometry. For both As （Ⅲ） and As （Ⅴ） the parameters such as NaBH4, HCI concentration, and pH were optimized. Absorption signal of As （Ⅴ） was approximately 17% of As （Ⅲ） signal. Therefore, for estimation of As （Ⅲ） and As （Ⅴ） concentrations in various samples the difference between the absorbance obtained for arsenic, without and with previous treatment of samples with potassium iodide （KI）, can be applied. The calibration graphs were linear （r〉0.99）, and the detection limits of the method based on three times the standard deviation of the blank were 0.14 and 0.64 μL^-1 for As （Ⅲ） and As （Ⅴ）, respectively. The relative standard deviation （R.S.D.） of measurements was less than 10%. As a means of checking performance method, water samples were spiked with known concentrations of both As （Ⅲ） and As （Ⅴ）, and recovery above 94% was obtained. The proposed method was applied successfully to determine inorganic As （Ⅲ） and As （Ⅴ） in various environmental and total As in biological samples.

Ameliorating Effect and Potential Mechanism of Camellia Oil on Constipated Mice

Constipation is a global epidemic. To evaluate the ameliorating effect of camellia oil on constipation,two slowtransit costive mice models were established by water deprivation or sucralfate gavage. Administration of camellia oil（ 4. 0 and 8. 0 mL/kg/day） significantly shortened the defecation time,increased defecation mass and fecal water content,with efficacies comparable to that of hemp seed oil. Intestinal propulsion test showed that camellia oil significantly enhanced the propelling rates of the charcoal powder in the intestine. Meanwhile,camellia oil also significantly decreased the serum levels of nitric oxide（ NO）,nitric oxide synthase（ NOS） and vasoactive intestinal peptide（ VIP） and increased serum substance P in costive animals. These results suggested that camellia oil can largely relieve slowtransit constipation and enhance the gastrointestinal motility through modulation of serum gastrointestinal motility key factors such as NO,NOS and VIP and substance P.

Chelation in Metal Intoxication XLVI:Synthesis of Someα-Mercapto-β-Substituted Aryl Acrylic Acids and TheirIn vitro Cadmium Chelating Ability

Objective To synthesize some new a-mercapto-β-substituted aryl acrylic acids, characterize them and investigate their in vitro cadmium chelating ability. Methods Six α-mercapto-β-substituted aryl acrylic acids were prepared by the alkaline hydrolysis of 5- (aryl methylene) rhodanines, obtained from the condensation of substituted aldehydes and rhodanine following the reported procedure. The new compounds were characterized by elemental analysis, infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy. The liver and kidney from cadmium chloride pre-administered rats were homogenized and their nuclear mitochondrial fraction (NMF) and supernatant cytosol fraction (SCF) were separated. A measured volume of each fraction was dialyzed separately using 'dialysis sack' against buffered-KCl medium containing a compound in the final concentration of 1×10-3 mol/L for 3 h at 37℃. The whole content of 'sack' was subjected to cadmium estimation following digestion with cone. Nitric acid was detected using flame atomic absorption spectrometer. Results The in vitro screening showed that α-mercapto-β-(p-methoxyphenyl) acrylic acid (compound 2) andα-mercapto-β-(m-methoxy, p-hydroxyphenyl) acrylic acid (compound 4) were more effective than α-mercapto-β-thienyl acrylic acid (compound 1) and a-mercapto-β-(p-dimethylaminophenyl) acrylic acid (compound 3) in mobilizing cadmium as their dialyzable chelates. The presence of a methoxy group on the phenyl moiety (compounds 2 and 4) increases the metal chelating ability of mercapto acrylic acids. Conclusions Compounds 2 and 4 seem to have accessibility to the cellular system and capability of chelating-out the intracellularly bound cadmium.

Proteomics analysis on hypolipidemic mechanisms of total phenylpropanoid glycosides from Ligustrum robustum(Roxb.) Blume in hamsters fed a high fat diet

OBJECTIVE To explore the hypolipidemic mechanisms of the total phenylpropanoid glycosides fromLigustrum robustum(Roxb.) Blume(LRTPG) in hamsters using proteomics technique.METHODS The hamsters were fed with a high fat diet to induce hyperlipidemia.Then LRTPG of high(1.2 g·kg^(-1)),medium(0.6 g·kg^(-1)) and low(0.3 g·kg^(-1)) doses were administrated daily for 4 weeks.Then the concentrations of plasma and hepatic lipids were determined using enzymic methods.The total protein was extracted from livers of the model group and the group treated with the high dose of LRTPG for label-free quantitative proteomics.RESULTS LRTPG significantly reduced the concentrations of plasma and hepatic lipids in hamsters fed a high fat diet.The proteomics data showed that a total of 2231 proteins were identified,and 549 proteins were found to be differentially expressed between the model group and the group treated with LRTPG.Among the 549 proteins,93 proteins were up-regulated and 59 proteins were down-regulated,and 397 proteins were absent or not.And some of these proteins were much related to the lipid metabolism.Further,gene ontology(GO) analysis indicated metabolic process,transport,oxidation-reduction process,phosphorylation,signal transduction,lipid metabolic process were the main biological processes that those differentially expressed proteins participated.KEGG pathway analysis showed that those proteins were involved in several metabolic pathways including oxidative phosphorylation,non-alcoholic fatty liver disease(NAFLD),PI3K-Akt signaling pathway,cAMP signaling pathway,cGMP-PKG signaling pathway.CONCLUSION The proteomics study could provide valuable clues to help us to understand the hypolipidemic mechanisms of LRTPG much better.

Doping Control Analysis of 16 Non-Steroidal Anti-Inflammatory Drugs in Equine Plasma Using Liquid Chromatography-Tandem Mass Spectrometry

Non-steroidal anti-inflammatory drugs (NSAIDs) are classified as Class 4 agents by the Association of Racing Commissioners International and are banned in racehorses during competition in Pennsylvania (PA). To control the abuse of these agents in racehorses competing in PA, a forensic method for screening and confirmation of the presence of these agents is needed. Equine plasma (0.5 mL) was acidified with 75 μL 1M H3PO4 to increase recovery of the analytes by liquid-liquid extraction using methyl tert-butyl ether (MTBE). Extracted analytes were separated by reversed-phase liquid chromatography using a C8 column under gradient condition. All 16 analytes were detected, quantified and confirmed using a triple quadrupole tandem mass spectrometry with selected reaction monitoring (SRM) in both negative and positive electrospray ionization modes. The limit of detection, quantification and confirmation of the analytes were 1.0 - 5.0 ng/mL, 1.0 - 5.0 ng/mL and 1.0 - 20 ng/mL, respectively. The linear dynamic range of quantification was 5.0 - 200 ng/mL. The method is routinely used in anti-doping analysis to control the abuse of NSAIDs in racehorses competing in PA.

Selection of Reference Genes in Equine White Blood Cells for Real Time PCR Normalization Following Extracorporeal Shock Wave Therapy

Selection of proper reference genes (RGs) is an essential step needed for accurate normalization of results from genomic studies. Expression of RGs is regulated by many factors such as species, age, gender, type of tissue, the presence of disease, and the administration of therapeutic treatment. The aim of the present study was to identify optimal RGs in a set of blood samples collected at different time points (0, 24, 48, 72 h) from horses following administration of extracorporeal shock wave therapy (ESWT). The mRNA expression of twelve RGs: HPRT1, ACTB, HSP90A, SDHA, GUSB, B2M, UBC, NONO, TBP, H6PD, RPL32, GAPDH was determined using real time quantitative polymerase chain reaction (qPCR). An SAS program developed on the algorithm of geNorm, SASqPCR, was used to determine stability of the expression and the number of optimal RGs. The results showed that the range of quantification cycle (Cq) values of the evaluated genes varied between 17 and 26 cycles, and that one optimal RG, ACTB, was sufficient for normalization of gene expression. Results of stability of expression demonstrated that ACTB was the optimal choice for all the samples studied. Notably, in samples collected at 72 h post ESWT, TBP showed a significant change in the expression level, and was not suitable for use as a RG. These results substantiate the importance of validating and selecting an appropriate RG.

Suspended particulate matter promotes epithelial-to-mesenchymal transition in alveolar epithelial cells via TGF-β1-mediated ROS/IL-8/SMAD3 axis

Epidemiological evidence presents that dust storms are related to respiratory diseases,such as pulmonary fibrosis(PF).However,the precise underlying mechanisms of SPM-elicited adverse effects still need to be investigated.Epithelial-mesenchymal transition(EMT)process is a characteristic of PF.We discussed whether suspended particulate matter(SPM)is involved in EMT induction via transforming growth factor-β1(TGF-β1).In this study,a detailed elemental analysis(55 elements),particle size,and morphology were determined.To investigate the toxicity of SPM,an MTT test was performed to detect cell viability.Next,A549cells were exposed to selected concentrations of SPM(20 and 40μg/mL)for single and repeated exposures.The DCFH-DA assay showed that exposure to SPM could produce reactive oxygen species(ROS).The ELISA assay demonstrated increased levels of interleukin-8(IL-8)and TGF-β1 in the supernatant.Western blot was used to detect the expression of proteins associated with EMT and the SMAD3-dependent pathway.Results of western blot demonstrated that E-cadherin was reduced,whereas p-SMAD3,vimentin,andα-smooth muscle actin were elevated.Our findings indicated that SPM triggered EMT by induction of oxidative stress,inflammation,and the TGF-β1/SMAD3 pathway activation.

A new ChatGPT-empowered,easy-to-use machine learning paradigm for environmental science

The quantity and complexity of environmental data show exponential growth in recent years.High-quality big data analysis is critical for performing a sophisticated characterization of the complex network of environmental pollution.Machine learning(ML)has been employed as a powerful tool for decoupling the complexities of environmental big data based on its remarkable fitting ability.Yet,due to the knowledge gap across different subjects,ML concepts and algorithms have not been well-popularized among researchers in environmental sustainability.In this context,we introduce a new research paradigm—“ChatGPT t ML t Environment”,providing an unprecedented chance for environmental researchers to reduce the difficulty of using ML models.For instance,each step involved in applying ML models to environmental sustainability,including data preparation,model selection and construction,model training and evaluation,and hyper-parameter optimization,can be easily performed with guidance from ChatGPT.We also discuss the challenges and limitations of using this research paradigm in the field of environmental sustainability.Furthermore,we highlight the importance of“secondary training”for future application of“ChatGPT t ML t Environment”.

Modulative effect of Physalis alkekengi on both gut bacterial and fungal micro-ecosystem

Objective: Gut microbiome is an intricate micro-ecosystem mediating the human health and drug efficacy. Physalis alkekengi(PAL) is an edible and time-honored traditional Chinese medicine. Several pharmacological effects of PAL have been verified and gut bacteria are implied in its therapeutic actions.However, the detailed modulation of PAL on gut bacterial species and on gut fungi remains largely unknown. We, therefore, designed a preliminary experiment in normal mice to reveal the modulation effect of PAL on both gut bacteria and fungi, and explore the interaction between them.Methods: Herein, the aqueous extract of PAL was orally administrated to normal C57BL/6 mice for four weeks. The full-length 16S rRNA and ITS1/2 gene sequencing were explored to detect the taxa of gut bacteria and gut fungi after PAL treatment, respectively.Results: Oral administration of PAL notably enriched anti-infammatory bacterial species such as Duncaniella spp. and Kineothrix alysoides, whereas decreased pro-infammatory species such as Mucispirillum schaedleri. Simultaneously, PAL increased the abundance of gut fungi Aspergillus ochraceus,Cladosporium sp. and Alternaria sp., and decreased Penicillium janthinellum. Correlation network analysis identified two co-existing microbial groups(groups 1 and 2) that were negatively associated with each other. The group 1 comprised PAL-enriched bacteria and fungi, while group 2 was mainly normal chow-enriched bacteria and fungi. In group 1, Antrodia monomitica, Aspergillus clavatus, Mortierella kuhlmanii and Sarcinomyces sp. MA 4787 were positively correlated with Bifidobacterium globosum,Romboutsia ilealis and so on. In group 2, Chaetomium subspirilliferum, Septoria orchidearum and Cephaliophora tropica were positively related to Lactobacillus spp.Conclusion: Altogether, this preliminary study first demonstrated the modulation effect of PAL on both gut bacteria and gut fungi, which may shed light on the elucidation of PAL’s pharmacological mechanism.

脂氧合酶介导的杀虫剂N-位脱甲基作用的体外实验

目的 探讨细胞色素P450加单氧酶系以外的代谢途径对杀虫剂的脱烷基作用 ,检测脂氧合酶 (LOX)介导的灭害威等的N 位脱甲基作用。方法 通过Nash反应检测大豆脂氧合酶 (SLO)对灭害威作用产生甲醛的量 ,反映其介导杀虫剂的N 位脱甲基反应速率。结果 SLO对灭害威的脱甲基作用与反应时间以及SLO浓度、灭害威和过氧化氢的浓度呈依赖关系。在最佳反应条件下 ,SLO产生甲醛的最大反应速度 (Vmax)为 1 8nmol·min- 1 ·nmol- 1 。SLO对灭害威的米氏常数 (Km)值为 3 .4mmol/L ,对过氧化氢的Km值为 2 35μmol/L。去甲二氢愈创木酸 (NDGA)、棉子醇 (gossypol)和芬宁东(phenidone)对脱甲基反应的强烈抑制作用提示 ,SLO起催化作用。还原型谷胱甘肽 (GSH)或二硫苏糖醇参与反应时 ,甲醛的累积量明显降低 ,表明SLO对灭害威脱甲基作用时 ,产生自由基。丁羟基甲苯(BHT)和丁羧基苯甲醚 (BHA)对甲醛的产生的抑制作用进一步支持这一论点。除灭害威外 ,发现其他的杀虫剂也发生N 位脱甲基作用 ,只是相对反应速率较低。

Cordycepin promotes browning of white adipose tissue through an AMP-activated protein kinase(AMPK)-dependent pathway

Obesity is a worldwide epidemic. Promoting browning of white adipose tissue(WAT)contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin(Cpn), a natural derivative of adenosine, increases energy expenditure, inhibits weight gain, improves metabolic profile and glucose tolerance, decreases WAT mass and adipocyte size, and enhances cold tolerance in normal and high-fat diet-fed mice. Cpn markedly increases the surface temperature around the inguinal WAT and turns the inguinal fat browner. Further investigations show that Cpn induces the development of brown-like adipocytes in inguinal and, to a less degree, epididymal WAT depots. Cpn also increases the expression of uncoupling protein 1(UCP1) and other thermogenic genes in WAT and3T3-L1 differentiated adipocytes, in which AMP-activated protein kinase(AMPK) plays an important role. Our results provide novel insights into the function of Cpn in regulating energy balance, and suggest a potential utility of Cpn in the treatment of obesity.

Gut Microbiota Brings a Novel Way to Illuminate Mechanisms of Natural Products in vivo

Poor bioavailability and undefined major/direct targets are two major obstacles for herbal medicines and natural products（NPs） to elucidate their precise mechanisms in vivo. Gut microbiota is an important bridge between eukayotic body and environment, which can interact with a majority of medicines with poor bioavailability and mediate their in vivo pharmacological activities. There are two main modes through which gut microbiota may mediate the pharmacological effects of NPs. First, gut microbiota catabolizes the NPs in herbal medicines into secondary metabolites with higher bioavialability and/or higher activity, facilitating the NPs enter circulation and exert beneficial impact at the pathological spot. Second, herbal medicines and NPs can favorably shift the compositional structure of gut microbiota, thereby performing remote functions to diseased organs/tissues via the systemic impaction of gut microbiota. In this review, the potential pathways were summarized through which gut microbes facilitate the pharmacological functions of herbal medicines and NPs and highlight the significance of gut microbiota in clarifying the in vivo mechanisms of herbal medicines and NPs.

Equisetin is an anti-obesity candidate through targeting 11β-HSD1

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin(EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate.We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1’s substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess11β-HSD1 products, EQST’s anti-obesity effects disappeared. Furthermore, EQST directly bond to11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.