Anti-N-methyl-D-aspartate receptor type autoimmune encephalitis with severe pneumonia:a case report

Autoimmune encephalitis(AE)is a type of encephalitis caused by autoimmune disease.AE was included on a list of the first batch of 121 rare diseases published by the Chinese National Health Commission on 11^(th)May 2018.Currently,patients with AE account for 10%-20% of encephalitis cases,with 54%-80% of those cases classified as the anti-N-methyl-D-aspartate receptor(NMDAR)type,which is the most common type.[1]In 2010,China reported the first case of a patient withanti-NMDARtype AE.

Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.METHODS Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were collected.Following fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™system.RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides distasonis.The functional prediction provided two different metabolic profiles between MASLD and LOLA.The 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis.The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.

Targeting TRPM2- and TRPM4-extrasynaptic N-methyl-D-aspartate receptor coupling in ischemic stroke

Ischemic stroke represents a heavy burden on public health.Currently,recanalization is the only effective therapy for ischemic stroke in a small population of eligible patients.However,there is no effective adjunct medication for preventing neuron loss after reperfusion to mitigate longlasting brain injury.Extrasynaptic N-methyl-Daspartate receptors (esNMDARs) are the major cause of ischemic neuronal death.However,there is no inhibitor selectively ta rgeting esNMDARs without compromising the function of other"beneficial"syna ptic NMDARs.

Determination of Carbon and Nitrogen Isotope Fractions in Asparagine, Aspartic Acid, Threonine and Methionine

The nomenclature for compounds that are modified with isotopes is growing every day. Compounds can be modified with isotopes either individually, in a functional group or groups, or completely with all atomic centers of the element. This diversity of isotope-modified compounds increases the range of researches that can be studied using them. Compounds modified with isotopes of carbon-13 or nitrogen-15 can be converted into carbon monoxide, carbon dioxide and molecular nitrogen. Currently, only the average value of carbon-13 or nitrogen-15 isotopes can be determined. However, by directly determining the atomic share of these isotopes in organic compounds modified with isotopes, information about the isotopic centers of the element can be obtained. The atomic fraction of an element is defined as a single carbon or nitrogen isotope-modified center or centers, or all centers that are isotope-modified with that element at the same time. Carbon-13 or nitrogen-15 isotopes’ atomic fraction can be determined molecularly or with fragment ions of different elemental content, or both. This makes the method self-verifying, increasing the accuracy and reliability of the results obtained. Amino acids, such as asparagine, aspartic acid, methionine, and threonine, are essential for the human body. This proposed method of isotopic analysis will increase the possibilities for scientific research using these compounds.

N-methyl-D-aspartate受体阻断剂MK801对离体海马脑片CA1区锥体细胞缺氧期间电生理的影响

目的 应用细胞内记录技术 ,研究 N- methyl- D- aspartate(NMDA)受体阻断剂 MK80 1对离体海马脑片 CA1区锥体细胞缺氧期间电生理的影响。方法 成年雄性 SD大鼠海马脑片随机分为单纯缺氧组 (Con组 ,n=1 0 )和 MK80 1组 (M组 ,n=1 0 )。Con组海马脑片给予 1 0分钟缺氧 ;而 M组的海马脑片在缺氧前 1 0分钟及 1 0分钟的缺氧期间分别应用 1 0 0 μmol/ L 的 MK80 1。所有脑片均给予 6 0分钟的复氧。应用细胞内记录技术记录海马 CA1区神经元缓慢去极化及快速去极化的时间、快速去极化的幅度。在复氧末 ,应用细胞内注入电流及经 Schaffer通路刺激 ,观察神经元对刺激的反应。结果 Con组海马 CA1区锥体神经元缓慢去极化速率为 (0 .2 2± 0 .0 5 ) m V/ s,显著高于 M组的 (0 .0 8± 0 .0 3) m V/ s (P<0 .0 5 ) ;NMDA受体阻断剂 MK80 1可以显著延迟神经元的快速去极化的时间 ,M组神经元的快速去极化时间为 (5 37± 1 39) s,显著高于 Con组的 (2 6 1± 2 6 ) s (P<0 .0 5 ) ;M组 CA1区神经元的快速去极化幅度为 (4± 1 3) m V,显著小于 Con组的 (5 3± 7) m V(P<0 .0 5 )。在复氧末 ,M组的 1 0例神经元中 ,9例神经元恢复对刺激的反应。结论 NMDA受体阻断剂可显著减轻神经元的缺氧性损伤 ,促进复氧后神经元功?

Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

Diagnostic value of FIB-4, aspartate aminotransferaseto-platelet ratio index and liver stiffness measurement in hepatitis B virus-infected patients with persistently normal alanine aminotransferase

AIM To assess the diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index(APRI), and liver stiffness measurement(LSM) in patients with hepatitis B virus infection who have persistently normal alanine transaminase(PNALT).METHODS We enrolled 245 patients with chronic hepatitis B: 95 in PNALT group, 86 in intermittently elevated alanine transaminase(PIALT1) group [alanine transaminase(ALT) within 1-2 × upper limit of normal value(ULN)], and 64 in PIALT2 group(ALT > 2 × ULN). All the patients received a percutaneous liver biopsy guided by ultrasonography. LSM, biochemical tests, and complete blood cell counts were performed.RESULTS The pathological examination revealed moderate inflammatory necrosis ratios of 16.81%(16/95), 32.56%(28/86), and 45.31%(28/64), and moderate liverfibrosis of 24.2%(23/95), 33.72%(29/86), and 43.75%(28/64) in the PNALT, PIALT1, and PIALT2 groups, respectively. The degrees of inflammation and liver fibrosis were significantly higher in the PIALT groups than in the PNALT group(P < 0.05). No significant difference was found in the areas under the curve(AUCs) between APRI and FIB-4 in the PNALT group; however, significant differences were found between APRI and LSM, and between FIB-4 and LSM in the PNALT group(P < 0.05 for both). In the PIALT1 and PIALT2 groups, no significant difference(P > 0.05) was found in AUCs for all comparisons(P > 0.05 for all). In the overall patients, a significant difference in the AUCs was found only between LSM and APRI(P < 0.05).CONCLUSION APRI and FIB-4 are not the ideal noninvasive hepatic fibrosis markers for PNALT patients. LSM is superior to APRI and FIB-4 in PNALT patients because of the influence of liver inflammation and necrosis.

High Temperature During Rice Grain Filling Enhances Aspartate Metabolism in Grains and Results in Accumulation of AspartateFamily Amino Acids and Protein Components

Global warming causes the exacerbation of rice growing environment, which seriously affects rice growth and reproduction, and finally results in the decrease of rice yield and quality. We investigated the activities of aspartate metabolism enzymes in grains, and the contents of Aspartate-family amino acids and protein components to further understand the effects of high temperature （HT） on rice nutritional quality during rice grain filling. Under HT, the average activities of aspartate aminotransferase （AAT） and aspartokinase （AK） in grains significantly increased, the amino acid contents of aspartate （Asp）, lysine （Lys）, threonine （Thr）, methionine （Met） and isoleucine （lie） and the protein contents of albumin, globulin, prolamin and glutelin also significantly increased. The results indicated that HT enhanced Asp metabolism during rice grain filling and the enhancement of Asp metabolism might play an important role in the increase of Asp-family amino acids and protein components in grains. In case of the partial appraisal of the change of Asp-family amino acids and protein components under HT, we introduced eight indicators （amino acid or protein content, ratio of amino acid or protein, amino acid or protein content per grain and amino acid or protein content per panicle） to estimate the effects of HT. It is suggested that HT during rice grain filling was benefit for the accumulation of Asp-family amino acids and protein components. Combined with the improvement of Asp-family amino acid ratio in grains under HT, it is suggested that HT during grain filling may improve the rice nutritional quality. However, the yields of parts of Asp-family amino acids and protein components were decreased under HT during rice grain filling.

Aspartate transaminase to platelet ratio index in hepatitis C virus and Schistosomiasis coinfection

AIM: To assess the diagnostic accuracy,of aminotransferase-to-platelet ratio index(APRI) alone and with antischistosomal antibody(Ab) in patients with hepatitis C virus(HCV) and schistosomiasis coinfection. METHODS: This retrospective study included medical records of three hundred and eighty three Egyptianmen patients who had undergone percutaneous liver biopsy between January 2006 to April 2014 in tertiary care hospital in Qatar for diagnosis or monitoring purpose were selected. Data of patients > 18 years of age were included in the study. The values of HCV RNA titer and antischistosomal antibody titer were also taken into consideration. Patients were excluded from the study if they had any other concomitant chronic liver disease,including; history of previous antiviral or interferon therapy,immunosuppressive,therapy,chronic hepatitis B infection,human immunodeficiency virus co-infection,autoimmune hepatitis,decompensated liver disease,hepatocellular carcinoma,prior liver transplantation,and if no data about the liver biopsy present. RESULTS: Median age of patients was 46 years. About 7.1% had no fibrosis,whereas 30.4%,37.5%,20.4%,and 4.6% had fibrosis of stage Ⅰ,Ⅱ,Ⅲ,and Ⅳ respectively. In bivariate analysis,APRI score,levels of AST,platelet count and age of patient showed statistically significant association with liver fibrosis(P < 0.0001); whereas antischistosomal antibody titer(P = 0.52) and HCV RNA titer(P = 0.79) failed to show a significant association. The respective AUC values for no fibrosis,significant fibrosis,severe fibrosis and cirrhosis of APRI score were 63%,73.2%,81.1% and 88.9% respectively. This showed good sensitivity and specificity of APRI alone for grading of liver fibrosis. But the inclusion of anti-Schistosoma antibody did not improve the prediction of fibrosis stage. CONCLUSION: The study results suggest that noninvasive biochemical markers like APRI are sensitive and specific in diagnosing the degree of fibrosis and cirrhosis in patients with coinfection of HCV and schistosomiasis as compared to biopsy. The addition of antischistosomal Ab to APRI did not improve sensitivity for predicting the degree of cirrhosis.

Mechanisms responsible for the effect of median nerve electrical stimulation on traumatic brain injuryinduced coma: orexin-A-mediated N-methyl-Daspartate receptor subunit NR1 upregulation

Electrical stimulation of the median nerve is a noninvasive technique that facilitates awakening from coma. In rats with traumatic brain injury-induced coma, median nerve stimulation markedly enhances prefrontal cortex expression of orexin-A and its receptor, orexin receptor 1. To further understand the mechanism underlying wakefulness mediated by electrical stimulation of the median nerve, we evaluated its effects on the expression of the N-methyl-D-aspartate receptor subunit NR1 in the prefrontal cortex in rat models of traumatic brain injury-induced coma, using immunohistochemistry and western blot assays. In rats with traumatic brain injury, NR1 expression increased with time after injury. Rats that underwent electrical stimulation of the median nerve（30 Hz, 0.5 ms, 1.0 m A for 15 minutes） showed elevated NR1 expression and greater recovery of consciousness than those without stimulation. These effects were reduced by intracerebroventricular injection of the orexin receptor 1 antagonist SB334867. Our results indicate that electrical stimulation of the median nerve promotes recovery from traumatic brain injury-induced coma by increasing prefrontal cortex NR1 expression via an orexin-A-mediated pathway.

Effects of Potassium Aspartate and Magnesium on Ventricular Arrhythmia in Ischemia-reperfusion Rabbit Heart

The aim of this study was to determine if the potassium aspartate and magnesium （PAM） prevent reperfusion-induced ventricular arrhythmias （RIVA） in ischemia-reperfusion （IR） rabbit heart. Thirty rabbits were randomly divided into control, ischemia and PAM groups. Arterially-perfused rabbit left ventricular preparations were made, and transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments. In control group rabbit ventricular wedge preparations were continuously perfused with Tyrode＇s solution, and in ischemia group and PAM groups the perfusion of Tyrode＇s solution was stopped for 30 min. Then the ischemia group was reperfused with Tyrode＇s solution and the PAM group with Tyrode＇s solution containing 2.42 mg/L PAM, respectively. ECG, QT interval, transmural repolarization dispersion （TDR） and action potentials from epicardium and endocardium were simultaneously recorded, and the RIVA of the wedge preparation was observed. Compared with control group, TDR and incidence of RIVA were significantly increased in ischemia group （P〈0.05）. The incidence of RIVA in control, ischemia and PAM group was 0/10, 9/10 and 1/10, respectively. Compared with ischemia group, TDR and incidence of RIVA were significantly reduced in PAM group （P〈0.05）. Potassium aspartate and magnesium significantly reduce TDR and prevent ventricular arrhythmia in ischemic rabbit heart.

Validation of aspartate aminotransferase to platelet ratiofor diagnosis of liver fibrosis and prediction of postoperativeprognosis in infants with biliary atresia

Validation of aspartate aminotransferase to platelet ratiofor diagnosis of liver fibrosis and prediction of postoperativeprognosis in infants with biliary atresia pathological Metavir fibrosis score of the liver wedgespecimens of 91 BA infants. The prognostic value ofpreoperative APRI for jaundice persistence, liver injury,and occurrence of cholangitis within 6 mo after KP wasstudied based on the follow-up data of 48 BA infants.RESULTS： APRI was significantly correlated withMetavir scores （rs = 0.433; P 〈 0.05）. The mean APRIvalue was 0.76 in no/mild fibrosis group （Metavir scoreF0-F1）, 1.29 in significant fibrosis group （F2-F3）, and2.51 in cirrhosis group （F4） （P 〈 0.001）. The areaunder the ROC curve （AUC） of APRI for diagnosingsignificant fibrosis and cirrhosis was 0.75 （P 〈 0.001）and 0.81 （P = 0.001）, respectively. The APRI cut-offof 0.95 was 60.6% sensitive and 76.0% specific forsignificant fibrosis diagnosis, and a threshold of 1.66was 70.6% sensitive and 82.7% specific for cirrhosis.The preoperative APRI in infants who maintainedjaundice around 6 mo after KP was higher than thatin those who did not （1.86 ± 2.13 vs 0.87 ± 0.48, P 〈0.05）. The AUC of APRI for prediction of postoperativejaundice occurrence was 0.67. A cut-off value of0.60 showed a sensitivity of 66.7% and a specificityof 83.3% for the prediction of jaundice persistence.Preoperative APRI had no significant association withlater liver injury or occurrence of cholangitis.CONCLUSION： Our study demonstrated that APRIcould diagnose significant liver fibrosis, especiallycirrhosis in BA infants, and the elevated preoperativeAPRI predicts jaundice persistence after KP.

Isolated elevated aspartate aminotransferase in an asymptomatic woman due to macro-aspartate aminotransferase: A case report

BACKGROUND Macro-aspartate aminotransferase(AST), a macroenzyme, is a high-molecular mass complex formed by self-polymerization or association with other serum components that are difficult for the kidney to clear, leading to the isolated elevation of serum AST activity. Cases of macro-AST formation are rare, with only 3 published in the English language literature up to September 2019 in China. In this paper, we present a case in which an asymptomatic woman with persistent isolated elevated AST was confirmed as having macro-AST by the polyethylene glycol precipitation method.CASE SUMMARY A 34-year-old woman was referred to our clinic for elevated AST levels with normal levels of other liver-associated enzymes on November 12, 2018. Her AST level of liver function test had been abnormal for 7 mo before she came to the clinic. The patient was asymptomatic with a normal physical examination. There was no relevant family history and no alcohol consumption or smoking. She had a several-month history of traditional Chinese medical taking and had stopped it 1 year prior. The laboratory tests in our clinic showed only the elevation of AST(89.5 U/L) with no other significant abnormalities. We performed the precipitation technique with polyethylene glycol to confirm the presence of macro-AST. Then for almost a year, her AST level still fluctuated in the abnormal range.CONCLUSION This case highlights that clinical physicians should be familiar with this rare condition of persistent isolated AST elevation due to the presence of macro-AST to avoid unnecessary investigation and patient anxiety.

Use of aspartate aminotransferase to platelet ratio to reduce the need for Fibro Scan in the evaluation of liver fibrosis

AIM To evaluate the performance of aspartate aminotransferase to platelet ratio(APRI) score against FibroS can in predicting the presence of fibrosis. METHODS Data of patients who concurrently had APRI score, Fibro Scan and liver biopsy to assess their hepatitis C virus(HCV) and hepatitis B virus(HBV) over 6 years were retrospectively reviewed and details of their disease characteristics and demographics were recorded. Advanced fibrosis was defined as ≥ F3. RESULTS Of the 3619 patients(47.5 ± 11.3 years, 97M:36F) who had Fibro Scans and APRI for HCV and HBV, 133 had concurrent liver biopsy. Advanced liver fibrosis was found in 27/133(20%, F3 = 21 and F4 = 6) patients. Although APRI score(P < 0.001, AUC = 0.83) and FibroS can(P < 0.001, AUC = 0.84) predicted the presence of advanced fibrosis, the sensitivities and specificities were only modest(APRI score: 51.9% sensitivity, 84.9% specificity; FibroS can: 63% sensitivity, 84% specificity). Whilst 13/27(48%) patients with advanced fibrosis had APRI ≤ 1.0, no patients with APRI ≤ 0.5 had advanced fibrosis, with100% sensitivity. The use of APRI ≤ 0.5 would avoid the need for FibroS can in 43% of patients. CONCLUSION APRI score and Fibro Scan performed equally well in predicting advanced fibrosis. A proposed APRI cutoff score of 0.5 could be used as a screening tool for FibroS can, as cut-off score of 1.0 will miss up to 48% of patients with advanced fibrosis. Further prospective validation studies are required to confirm this finding.

The Characteristics of Biophotonic Activity Induced by Aspartate May Be Related to the Evolution of Species

Glutamate, the most abundant excitatory neurotransmitter in the nervous system, can induce biophotonic activity and transmission in mouse brain slices. As a signaling molecule, aspartate is not considered to be an independent neurotransmitter during the long evolution process, which may be just a co-transmitter or neuromodulator. In the view of structure and physiological similarities of aspartate and glutamate, as well as some differences between them, we attempted to investigate whether aspartate could also induce biophotonic activity in mouse brain slices and its effect characteristics. The ultraweak biophoton imaging system (UBIS) was used to carry out a real-time observation of biophoton activity induced by aspartate in mouse brain slices. It was found that the biophotonic emissions induced by aspartate at different concentrations (12.5 mM, 25 mM and 50 mM) presented concentration-dependent effects and 50 mM aspartate could obviously induce biophoton activities with the characteristic changes of initiation, maintenance, washing and reapplication, which were also different from that induced by 50 mM glutamate as reported before. Considering the species differences in excitatory neurotransmitters, these findings indicate that aspartate-induced biophotonic activity may imply the evolutionary differences in the animal brains.

Aspartate transferase-to-platelet ratio index-plus: A new simplified model for predicting the risk of mortality among patients with COVID-19

BACKGROUND Coronavirus disease 2019(COVID-19)has a spectrum of clinical syndromes with serious involvement of the lung and frequent effection of the liver and hemostatic system.Blood biomarkers are affordable,rapid,objective,and useful in the evaluation and prognostication of COVID-19 patients.AIM To investigate the association between aspartate transferase-to-platelet ratio index(APRI)and in-hospital mortality to develop a COVID-19 mortality prediction model.METHODS A multicenter cohort study with a retrospective design was conducted.Medical records of all consecutive adult patients admitted to Al-Azhar University Hospital(Assiut,Egypt)and Chest Hospital(Assiut,Egypt)with confirmed COVID-19 from July 1,2020 to October 1,2020,were retrieved and analyzed.The patient cohort was classified into the following two categories based on the APRI:(1)COVID-19 presenting with APRI≤0.5;and(2)COVID-19 presenting with APRI(>0.5 and≤1.5).The association between APRI and all-cause in-hospital mortality was analyzed,and the new model was developed through logistic regression analyses.RESULTS Of the 353 patients who satisfied the inclusion criteria,10%were admitted to the intensive care unit(n=36)and 7%died during the hospital stay(n=25).The median age was 40 years and 50.7%were male.On admission,49%had aspartate transferase-dominant liver injury.On admission,APRI(>0.5 and≤1.5)was independently associated with all-cause in-hospital mortality in unadjusted regression analysis and after adjustment for age and sex;after stepwise adjustment for several clinically relevant confounders,APRI was still significantly associated with all-cause inhospital mortality.On admission,APRI(>0.5 and≤1.5)increased the odds of mortality by fivetimes(P<0.006).From these results,we developed a new predictive model,the APRI-plus,which includes the four predictors of age,aspartate transferase,platelets,and serum ferritin.Performance for mortality was very good,with an area under the receiver operating curve of 0.90.CONCLUSION APRI-plus is an accurate and simplified prediction model for mortality among patients with COVID-19 and is associated with in-hospital mortality,independent of other relevant predictors.

Alanine and aspartate aminotransferase and glutamine-cycling pathway:Their roles in pathogenesis of metabolic syndrome

Although new research technologies are constantly used to look either for genes or biomarkers in the prediction of metabolic syndrome(MS),the pathogenesis and pathophysiology of this complex disease remains a major challenge.Interestingly,Cheng et al recently investigated possible pathways underlying MS by high-throughput metabolite profiling in two large and well characterized community-based cohorts.The authors explored by liquid chromatography and mass spectrometry the plasma concentrations of 45 distinct metabolites and examined their relation to cardiometabolic risk,and observed that metabolic risk factors such as obesity,insulin resistance(IR),high blood pressure,and dyslipidemia were associated with several metabolites,including branched-chain amino acids,other hydrophobic amino acids,tryptophan breakdown products,and nucleotide metabolites.In addition,the authors found a significant association of IR traits with glutamine,glutamate and the glutamineto-glutamate ratio.These data provide new insight into the pathogenesis of MS-associated phenotypes and introduce a crucial role of glutamine-cycling pathway as prominently involved in the development of metabolic risk.We consider that the hypothesis about the role of abnormal glutamate metabolism in the pathogenesis of the MS is certainly challenging and suggests the critical role of the liver in the global metabolic modulation as glutamate metabolism is linked with aminotransferase reactions.We discuss here the critical role of the "liver metabolism" in the pathogenesis of the MS and IR,and postulate that before fatty liver develops,abnormal levels of liver enzymes,such as alanine and aspartate aminotransferases might reflect high levels of hepatic transamination of amino acids in the liver.

Serum γ-glutamyltransferase,alanine aminotransferase,and aspartate aminotransferase activity in Iranian healthy blood donor men

AIM: To determine serum γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity, and to assess their correlation with demographic and clinical findings in healthy blood donors. METHODS: This cross-sectional study was performed in 934 male blood donors, aged 18 to 68 years, who consecutively attended Tehran blood transfusion service in 2006. All participants were seronegative for HBV or HCV infections, non alcohol users, and all underwent a standard interview and anthropometric tests. Clinical and biochemical parameters including AST, ALT, and GGT activities were determined. Patients taking drugs known to cause hepatic fat deposition were excluded. For AST, ALT, and GGT variables, we used 33.33 and 66.66 percentiles, so that each of them was divided into three tertiles. RESULTS: Mean AST, ALT, and GGT activities were 25.26 ± 12.58 U/L (normal range 5-35 U/L), 33.13 ± 22.98 (normal range 5-35 U/L), and 25.11 ± 18.32 (normal range 6-37 U/L), respectively. By univariate analyses, there were significant associations between increasing AST, ALT, or GGT tertiles and age, body weight, body mass index, and waist and hip circumferences (P < 0.05). By multiple linear regression analyses, ALT was found to be positively correlated with dyslipidemia (B = 6.988, P = 0.038), whereas ALT and AST were negatively correlated with age. AST, ALT, and GGT levels had positive correlation with family history of liver disease (B = 15.763, P < 0.001), (B = 32.345, P < 0.001), (B =24.415, P < 0.001), respectively.CONCLUSION: Although we did not determine the cutoffs of the upper normal limits for AST, ALT, and GGT levels, we would suggest screening asymptomatic patients with dyslipidemia and also subjects with a family history of liver disease.

Treatment of chronic hepatitis B patients with tyrosinemethionine-aspartate-aspartate mutations

Lamivudine is an antiviral used for the treatment of chronic hepatitis B. Several studies have reported various mutations that are induced by lamivudine therapy. These mutations in the tyrosine-methionineaspartate-aspartate(YMDD) motif are necessary and sufficient to confer high-level lamivudine resistance. During treatment with lamivudine, mutations develop in the YMDD motif of the hepatitis B virus(HBV) polymerase gene and lamivudine cannot prevent the replication of the mutant form. The virulence strain of developed mutation in the polymerase gene is lower than the original virus and they are susceptible to treatment with some other nucleoside analogs except lamivudine. Entecavir and tenofovir are potent HBV inhibitors and they can be confidently used as first line monotherapies. We read the article written by Tan et al that lamivudine therapy improved the clinical course in HBV patients with natural YMDD mutations. We think that lamivudine use for this patient group is not appropriate. These patients should use YMDD mutant form-effective drugs such as adefovir, tenofovir.

Determination of the upper cut-off values of serum alanine aminotransferase and aspartate aminotransferase in Chinese

AIM:To determine the upper cut-off values of serumalanine aminotransferase(ALT)and aspartate aminotransferase(AST)in a Northern Chinese population.METHODS:A total of 3769 subjects in Jilin Province Northeast China were stratified to determine the potential factors affecting serum ALT and AST levels.The upper cut-off values of serum ALT and AST in these subjects were determined using receiver operating characteristic analysis and their sensitivity and specificity were evaluated.RESULTS:Stratification analysis revealed that serum ALT and AST levels were associated with gender,alcohol consumption,serum cholesterol and triglyceride levels,and body mass index.The upper cut-off values of serum ALT and AST were 22.15 U/L and 25.35 U/L for healthy men and 22.40 U/L and 24.25 U/L for healthy women,respectively.The new cut-off values had a higher sensitivity,but a slightly lower specificity than the current standards.CONCLUSION:Our results indicate that the new upper cut-off values of serum ALT and AST are markedly lower than current standards and may be valuable for the evaluation of liver function.