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.

Effects of the Amino Acids of Aspartate Family on the Biosynthesis of CoQ_(10) in Rhodopseudomonas palustris J001

[Objective]The study aimed to investigate the effects of the amino acids of aspartate family on the biosynthesis of CoQ10 in Rhodpseudomonas palustris J001.[Method]The impacts of amino acids of this family on the biosynthesis of CoQ10 in Rhodopseudomnas palustris J001 were investigated by feeding these amino acids at the end of the logarithmic phase during incubation,which aim was for the optimization of the fermentation medium and genetic improvement of the strain for CoQ10 production.[Result]The results showed that feeding proper amount of methione(125 mg/L)could increase CoQ10 production by 20.2%,but feeding of lysine(above 500 mg/L),threonine(above 400 mg/L)and/or isoleucine(above 400 mg/L)repressed the biosynthesis of CoQ10.The results indicated that the aspartate kinase is subject to feedback inhibition or repression by lysine,threonine and isoleucine in the strain,which was unfavorable to the formation of methioine and then caused the decrease of CoQ10 production.[Conclusion]Lysine,threonine and isoleucine auxotrophic mutants with resistance to analogues of lysine,threonine and isoleucine could increase the production of CoQ10.

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.

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.

Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

BACKGROUND： Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE： To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY： A computer-based online search was conducted in PUBMED for English language publications containing the key words ＂brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor＂ from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria： ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria： duplicated articles. LITERATURE EVALUATION： References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS： After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these factors change at different time points after brain injury, and what is the relationship between associated factors and cognitive disorder. CONCLUSION： It is necessary to comprehensively study some associated factors, to analyze their changes and their relationship with cognitive disorder following brain injury, and to investigate their effects at different time points after brain injury.

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.

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.

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.

Disproportional exaggerated aspartate transaminase is a useful prognostic parameter in late leptospirosis

AIM: To evaluate the hepatic dysfunction in leptospirosis is usually mild and resolved eventually. However,sequential follow-up of liver biochemical data remained lacking..METHODS: The biochemistry data and clinical symptoms of 11 sporadic patients were collected and analyzed, focusing on the impacts of leptospirosis upon liver biochemistry tests.RESULTS: The results disclosed that of the 11 cases, 5 or 45% died. The liver biochemistry data in the beginning of the disease course were only mildly elevated.Nevertheless, late exaggerated aspartate transaminase (AST)elevations were noted in three cases who finally died when compared with the typical course. Besides, significant higher AST/alanine transaminase (ALT) ratios (AARs) of the peak levels for transaminase were also noted in the cases who eventually succumbed. The mean±SD of AARs for the survival group and dead group were 5.65±2.27 (n = 5)and 1.86±0.64 (n = 6) respectively (P= 0.006). The ratios of the cases who finally died were all more than 3.0.Conversely, the survival group's ratios were less than 3.0.CONCLUSION: Serial follow-up of transaminase might provide evidence to predict some rare evolutions in leptospirosis. If AST elevated progressively without a concomitant change of ALT, it might indicate an acute disease course with ensuing death. Additionally, AAR is another prognostic parameter for leptospirosis. Once the value was higher than 3.0, a grave prognosis is inevitable.

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.

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

To evaluate the performance of aspartate aminotransferase to platelet ratio (APRI) score against FibroScan in predicting the presence of fibrosis. METHODSData of patients who concurrently had APRI score, FibroScan 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. RESULTSOf the 3619 patients (47.5 ± 11.3 years, 97M:36F) who had FibroScans 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 FibroScan (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; FibroScan: 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, with 100% sensitivity. The use of APRI ≤ 0.5 would avoid the need for FibroScan in 43% of patients. CONCLUSIONAPRI score and FibroScan performed equally well in predicting advanced fibrosis. A proposed APRI cut-off score of 0.5 could be used as a screening tool for FibroScan, 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.

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.

Development of Enzyme Biosensor for Amperometric Measurement of Aspartate Aminotransferase

An enzyme biosensor for amperometric measurement of aspartate aminotransferase has been developed.The working electrode was modified with a thin-film of redox polymer,then glutamate oxidase,with the immobilized reagent cast and dried on the electrode.The biosensor responses to AST by detecting hydrogen peroxide were produced by enzymical reaction at-0.1 V with a response time of 120 seconds.The electrode gave a detection limit of 32.5 U/L with a linear concentration range of 32.5 U/L～2000 U/L in serum.Due to more sensitive and lower detection limit,the biosensor is expected mainly to be used for physiological identification and physical performance of athletes in the future.Extended application will also affect the practice of clinical medicine for the diagnosis of heart and liver disease.

Effects of Fuzheng Huayu Capsules combined with nucleoside antiviral drugs on liver and kidney function, serum inflammatory factors, TLR-4, TGF-β1 and aspartate aminotransferase-platelet ratio index in patients with HBV infection and decompensated liver

Objective:To investigate the effect of Fuzheng Huayu Capsule combined with nucleoside antiviral drugs on liver and kidney function,serum inflammatory factors,Toll-like receptor 4(TLR-4),transforming growth factorβ1(TGF-β1)And aspartate aminotransferase-platelet ratio index(APRI).Methods:A total of 144 patients with HBV infection and decompensated cirrhosis were selected.All patients were divided into control group and case group by random number table method,with 72 cases in each group.The control group was given conventional liver protection and antiviral therapy;the case group was supplemented with Fuzheng Huayu Capsule on the basis of treatment in the control group.The changes of liver and kidney function,serum inflammatory factors,TLR-4,TGF-β1 and APRI in the two groups were observed.Results:The total effective rate of the case group was 93.06%,higher than 76.32%of the control group(P<0.05).Case group HBV DNA negative rate,negative rate of hepatitis B virus surface antigen(HBsAg),negative rate of hepatitis B virus e antigen(HBeAg)were significantly higher than the control group(76.39%vs 59.72%,55.56%vs 31.94%,51.39%vs 29.17%),the difference was statistically significant(P<0.05).Alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),hyaluronic acid(HA),laminin(LN),typeⅢprocollagen after treatment(PCⅢ),typeⅣcollagen(CⅣ),inner diameter of portal vein,inner diameter of splenic vein,spleen thickness,resistance index,urea nitrogen(BUN),creatinine(Cr),interleukin-6(IL-6),interleukin-8(IL-8),high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),TLR-4,TGF-β1,APRI are lower than before treatment,albumin(ALB)and renal blood The flow rate was higher than before treatment;liver function indicators,liver fibrosis indicators,liver and spleen imaging indicators,renal hemodynamic indicators,serum inflammatory factors,TLR-4 in the case group The improvement of TGF-β1 and APRI.Conclusion:Fuzheng Huayu Capsules combined with nucleoside antiviral drugs have a clear clinical effect on patients with HBV infection and decompensated liver cirrhosis,significantly improve the clinical symptoms of patients,improve liver and kidney function,reduce inflammatory factor production,and can effectively inhibit HBV replication.Certain promotion value is worthy of further clinical research.

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.

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.

Identification of key residues for the activity of aspartate 4‑decarboxylase towards l‑3‑methylaspartate

Aspartate 4-decarboxylase(ASD)has been modified to obtain the catalytic ability of the unnatural substrate l-3-methylaspartate.However,the mechanism remains to be clarified.In the present study,the semi-rational modification was used to identify key residues of importance for the activity towards l-3-methylasparte.The ASD from Pseudomonas dacunhae 21192(PdASD)was used as a template,which showed better activity than the other two ASDs.Four residues proved to be critical for the activity towards l-3-methylasparte,with three located in the active site and one on the surface.Combinatorial variants were constructed to analyze the role of each mutation.The enzymatic properties of the combined variants were determined and compared.The residue at the 17th position was a member of the substrate entrance gate and contributed to the activity by reducing the steric hindrance.The residue at the 37th position was necessary for activity.Two mutations,I288 and V382,exhibited strong epistatic interactions on the activity of ASD.Structural changes in the active site were analyzed by molecular dynamics simulations,and it is proposed that the increased activity of PdASD variants is related to a suitable binding pocket for the substrate.These results provide new evidence for the mechanism ofβ-decarboxylation,which lays the foundation for enhancing the activity of ASD.

载药微球联合TACE治疗原发性肝癌患者的效果观察

目的观察载药微球联合肝动脉化疗栓塞术(TACE)治疗原发性肝癌患者的效果。方法选取2021年6至12月收治的原发性肝癌患者60例,根据患者住院序号分为研究组和对照组各30例。研究组采用TACE联合CalliSpheres载药微球治疗,对照组接受传统TACE治疗。观察2组临床疗效、血常规、肝功能指标、甲胎蛋白(AFP)水平,并评估安全性。结果2组治疗后血红蛋白、血小板计数、白蛋白较治疗前降低,总胆红素、丙氨酸转氨酶、天冬氨酸转氨酶较治疗前升高(P<0.05);2组治疗后1周上述指标比较差异无统计学意义(P>0.05)。研究组治疗后AFP水平低于对照组(P<0.05)。研究组并发症及毒副反应发生率低于对照组(P<0.05)。研究组总有效率[86.67%(26/30)]高于对照组[63.33%(19/30)](P<0.05)。研究组术后1、2年的总体生存与局部控制率均高于对照组(P<0.05)。研究组满意度评分[(79.14±16.37)分]高于对照组[(64.35±17.22)分](P<0.01)。结论载药微球联合TACE治疗原发性肝癌效果较好,可有效延长患者生存时间,减轻并发症及毒副反应,提高生存质量。