OBJECTIVE To investigate the effect of N-methyl-D-aspartic acid(NMDA)receptor in the secondary visual cortex(V2)on methamphetamine-associated contextual learning and memory.METHODS With male C57BL/6J mice as subjects and using the mouse conditioned place preference(CPP)experiment,the scores of CPP were observed after microinjection of NMDA receptor selective antagonist D-AP5(0.5 μg per side)into the bilateral V2 during the formation phase,single microinjec-tion of D-AP5(0.5 μg per side)into the bilateral V2 prior to the expression test,and methamphetamine(0.5 mg·kg-1,ip)-induced reactivation test and methamphetamine-associated contextual-induced reacti-vation test,to evaluate the effect of NMDA receptors on the formation,expression and reinstatement of methamphetamine-induced CPP.RESULTS Compared with the control group,microinjection of D-AP5(0.5 μg per side)into the bilateral V2 during the formation phase did not have significant inhibitory effect on CPP scores,nor did single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to the expression test,single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to metham-phetamine(0.5 mg·kg-1,ip)-induced reactivation test or single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to methamphetamine-associated contextual-induced reactivation test.CONCLU-SION The NMDA receptor in the V2 is not involved in the formation,expression and reactivation of meth-amphetamine-associated contextual learning and memory.

As the use of nursing information systems (NIS) in clinical nursing practice has proliferated, NIS education has received increased attention. This paper introduces the background and research form of NIS in nursing education at home and abroad, and summarizes the deficiencies in the application and puts forward suggestions, in order to provide references for the subsequent development of a high-quality system and the development of courses that fit the actual situation of nursing students in China.

OBJECTIVE To investigate the protective effects of hydroxytyrosol hydroxybutyrate(HTHB)against cognitive impairment induced by acute sleep deprivation in mice and to explore the underlying mechanisms.METHODS Male C57BL/6J mice were assigned to the following groups:normal control,normal groups administered with HTHB 30,60 and 120 mg·kg-1 or hydroxytyrosol(HT 19.25,38.5 and 77 mg·kg-1),a sleep deprivation(SD)model group,and SD groups co-administered with the same doses of HTHB or HT.Acute sleep deprivation was induced for 72-96 h using a rotarod apparatus in all groups except the normal control and normal drug-treated groups.Based on dose-response assess-ments in the Y-maze and novel object recognition tests,the effective doses(HTHB 60 mg·kg-1 and HT 38.5 mg·kg-1)were selected for subsequent evaluation in the two-choice visual discrimination task that was performed in a subset of groups:normal control,normal+HTHB 60 mg·kg-1,normal+HT 38.5 mg·kg1,SD model,SD+HTHB 60 mg·kg-1,and SD+HT 38.5 mg·kg-1.Cognitive functions that were assessed included spatial working memory(Y-maze spontaneous alternation),object recognition memory(novel object recognition)and visual discrimination ability(two-choice visual discrimination task).Biochemically,levels of hippocampal reactive oxygen species(ROS)were quantified by ELISA while the ATP content was determined using a firefly luciferase-based assay.RESULTS In non-sleep-deprived mice,neither HTHB nor HT administration significantly altered locomotor activity,spatial working memory,object recognition memory,or visual discrimination performance.Following sleep deprivation,the model group displayed significant cognitive deficits,including reduced spontaneous alternation rate,lower novel object recognition indexes,and decreased accuracy in the visual discrimination task at 48 and 96 h.These impairments were accompanied by elevated hippocampal ROS levels and reduced ATP contents com-pared to the control group.Treatment with HT 38.5 and 77 mg·kg-1 significantly attenuated the deficit in spontaneous alternation,but did not affect other parameters.In contrast,HTHB at 60 and 120 mg·kg-1 produced broader restorative effects and significantly reversed impairment in both spontaneous alterna-tion and novel object recognition.Furthermore,HTHB at 60 mg·kg-1 significantly improved visual discrimination accuracy at 48 and 96 h,while lowering hippocampal ROS levels and increasing ATP contents.CONCLUSION HTHB effectively mitigates acute sleep deprivation-induced impairment in spatial working memory,object recognition memory,and visual discrimination in mice.This protection is likely mediated by the enhancement of mitochondrial antioxidant capacity and the restoration of energy metabolism.

OBJECTIVE To investigate the protective effects of hydroxytyrosol hydroxybutyrate(HTHB)against cognitive impairment induced by acute sleep deprivation in mice and to explore the underlying mechanisms.METHODS Male C57BL/6J mice were assigned to the following groups:normal control,normal groups administered with HTHB 30,60 and 120 mg·kg-1 or hydroxytyrosol(HT 19.25,38.5 and 77 mg·kg-1),a sleep deprivation(SD)model group,and SD groups co-administered with the same doses of HTHB or HT.Acute sleep deprivation was induced for 72-96 h using a rotarod apparatus in all groups except the normal control and normal drug-treated groups.Based on dose-response assess-ments in the Y-maze and novel object recognition tests,the effective doses(HTHB 60 mg·kg-1 and HT 38.5 mg·kg-1)were selected for subsequent evaluation in the two-choice visual discrimination task that was performed in a subset of groups:normal control,normal+HTHB 60 mg·kg-1,normal+HT 38.5 mg·kg1,SD model,SD+HTHB 60 mg·kg-1,and SD+HT 38.5 mg·kg-1.Cognitive functions that were assessed included spatial working memory(Y-maze spontaneous alternation),object recognition memory(novel object recognition)and visual discrimination ability(two-choice visual discrimination task).Biochemically,levels of hippocampal reactive oxygen species(ROS)were quantified by ELISA while the ATP content was determined using a firefly luciferase-based assay.RESULTS In non-sleep-deprived mice,neither HTHB nor HT administration significantly altered locomotor activity,spatial working memory,object recognition memory,or visual discrimination performance.Following sleep deprivation,the model group displayed significant cognitive deficits,including reduced spontaneous alternation rate,lower novel object recognition indexes,and decreased accuracy in the visual discrimination task at 48 and 96 h.These impairments were accompanied by elevated hippocampal ROS levels and reduced ATP contents com-pared to the control group.Treatment with HT 38.5 and 77 mg·kg-1 significantly attenuated the deficit in spontaneous alternation,but did not affect other parameters.In contrast,HTHB at 60 and 120 mg·kg-1 produced broader restorative effects and significantly reversed impairment in both spontaneous alterna-tion and novel object recognition.Furthermore,HTHB at 60 mg·kg-1 significantly improved visual discrimination accuracy at 48 and 96 h,while lowering hippocampal ROS levels and increasing ATP contents.CONCLUSION HTHB effectively mitigates acute sleep deprivation-induced impairment in spatial working memory,object recognition memory,and visual discrimination in mice.This protection is likely mediated by the enhancement of mitochondrial antioxidant capacity and the restoration of energy metabolism.

OBJECTIVE To investigate the effect of N-methyl-D-aspartic acid(NMDA)receptor in the secondary visual cortex(V2)on methamphetamine-associated contextual learning and memory.METHODS With male C57BL/6J mice as subjects and using the mouse conditioned place preference(CPP)experiment,the scores of CPP were observed after microinjection of NMDA receptor selective antagonist D-AP5(0.5 μg per side)into the bilateral V2 during the formation phase,single microinjec-tion of D-AP5(0.5 μg per side)into the bilateral V2 prior to the expression test,and methamphetamine(0.5 mg·kg-1,ip)-induced reactivation test and methamphetamine-associated contextual-induced reacti-vation test,to evaluate the effect of NMDA receptors on the formation,expression and reinstatement of methamphetamine-induced CPP.RESULTS Compared with the control group,microinjection of D-AP5(0.5 μg per side)into the bilateral V2 during the formation phase did not have significant inhibitory effect on CPP scores,nor did single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to the expression test,single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to metham-phetamine(0.5 mg·kg-1,ip)-induced reactivation test or single microinjection of D-AP5(0.5 μg per side)into the bilateral V2 prior to methamphetamine-associated contextual-induced reactivation test.CONCLU-SION The NMDA receptor in the V2 is not involved in the formation,expression and reactivation of meth-amphetamine-associated contextual learning and memory.

As the use of nursing information systems (NIS) in clinical nursing practice has proliferated, NIS education has received increased attention. This paper introduces the background and research form of NIS in nursing education at home and abroad, and summarizes the deficiencies in the application and puts forward suggestions, in order to provide references for the subsequent development of a high-quality system and the development of courses that fit the actual situation of nursing students in China.

Objective:To investigate the clinical manifestations, pathological, and gene mutation characteristics of ABCB4 gene variant-associated cholestatic liver disease in adults. Methods:Eight adult cases of ABCB4 gene variant-associated cholestatic liver disease who were hospitalized in the Department of Hepatology, Fifth Medical Center of the People's Liberation Army General Hospital from May 2010 to December 2022 were enrolled in this study. The clinical manifestations, pathological features, gene variant features, and prognostic conditions were analyzed. Patient gene testing and biological information analysis were performed using whole-exome next-generation sequencing. SPSS 19.0 software was used to conduct descriptive analysis. Results:Among the eight adult cases of the ABCB4 gene variant, there were three males and five females, with a median age of onset of 24 (20, 37) years. There were three cases with a compound heterozygous variant in ABCB4, and the clinical phenotypes included two cases of progressive familial intrahepatic cholestasis type 3 and one case of intrahepatic cholestasis of pregnancy overlapping with low-phospholipid-associated cholelithiasis syndrome. There were five cases with a single heterozygous variant in ABCB4, and the clinical phenotypes included two cases of intrahepatic cholestasis of pregnancy overlapping with drug-induced liver injury and three cases of low-phospholipid-associated cholelithiasis syndrome. Imaging of all eight cases showed liver fibrosis, and six cases already had cirrhosis. All patients underwent liver histopathological examination, which mainly showed cholestasis and portal fibrosis in eight cases, small bile duct hyperplasia in seven cases, copper deposition in three cases, and cirrhosis in five cases. ABCB4 screening revealed 11 different mutations, including eight new mutations. The pathogenicity assessment showed that c.2394+82C>T (intron) was a benign mutation, and the rest were deleterious mutations. Ursodeoxycholic acid was the treatment for all patients, with a follow-up time of 7.5 (0.5, 12.7) years. One case died of end-stage liver disease, two cases developed cholestatic cirrhosis, and five cases were in stable condition. Conclusion:The adult ABCB4 gene variant-associated cholestatic liver disease are mostly single heterozygous mutations, the clinical phenotypes are diverse and overlapping, the disease is more severe in those who carried non-functional mutations.

Objective To analyze the correlation between serum soluble Klotho protein(sKL)and tendino-C(TN-C)and the severity of disease and oxidative stress in children with immunoglobulin A(IgA)nephropa-thy.Methods A total of 85 children with IgA nephropathy admitted to the hospital from July 2019 to August 2022 were selected as IgA nephropathy group,and 85 healthy patients who underwent physical examination in the hospital during the same period were selected as healthy group.Serum sKL and TN-C levels were com-pared between the two groups.Receiver operating characteristic(ROC)curve was drawn to analyze the value of serum sKL,TN-C and their combination in predicting the occurrence of IgA nephropathy.IgA nephropathy group was divided into mild group(28 cases),moderate group(39 cases)and severe group(18 cases)accord-ing to 24 h urinary protein quantity.Serum sKL,TN-C levels and oxidative stress indexes[malondialdehyde(MDA),superoxide dismutase(SOD)and advanced oxidation protein product(AOPP)]of the three groups were compared.The correlation between serum sKL and TN-C levels and oxidative stress indexes was ana-lyzed by Spearman correlation,and the correlation between serum sKL and TN-C levels and the severity of IgA nephropathy in children was examined by Kendall's Tau-b.Results The serum sKL level in IgA ne-phropathy group was lower than that in healthy group,and the serum TN-C level was higher than that in healthy group,the difference was statistically significant(P＜0.05).ROC curve showed that the area under the curve and 95％CI of serum sKL,TNC and their combination predicted the occurrence of IgA nephropathy were 0.726(95％CI:0.648-0.803),0.853(95％CI:0.796-0.909)and 0.891(95％CI:0.845-0.937).The level of serum sKL in severe group was lower than that in moderate and mild groups,while the level of serum TN-C was higher than that in moderate and mild groups,and the difference was statistically significant(P＜0.05).The serum SOD level of severe group was lower than that of moderate group and mild group,and the serum AOPP and MDA levels were higher than those of moderate group and mild group,the difference was statistically significant(P＜0.05).Spearman correlation showed that sKL level was positively correlated with SOD(r＞0,P＜0.05),and negatively correlated with AOPP and MDA(r＜0,P＜0.05).TN-C level was negatively correlated with SOD(r＜0,P＜0.05),and positively correlated with AOPP and MDA(r＞0,P＜0.05).Conclusion The levels of serum sKL and TN-C in children with IgA nephropathy are related to the severity of disease and oxidative stress,and the combination of SKL and TN-C can effectively predict the occurrence of IgA nephropathy.

Objective To investigate the liver disease phenotypes and clinical features of patients with different genotypes of Wilson's disease(WD).Methods A retrospective analysis was performed for 163 patients with WD who were diagnosed and underwent genetic testing in The Fifth Medical Center of Chinese PLA General Hospital from August 2008 to June 2023,and clinical manifestations,laboratory examination,pathological examination,imaging examination,and ATP7B genetic testing results were collected.According to ATP7B gene mutation,the patients were divided into groups as follows:R778L mutation group and non-R778L mutation group;P992L mutation group and non-P992L mutation group;truncation mutation group and non-truncation mutation group.Liver disease phenotypes and clinical features were analyzed for the patients with c.2333G>T/p.R778L mutation(R778L mutation),c.2975C>T/p.P992L mutation(P992L mutation),and truncation mutation of the ATP7B gene.The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of continuous data between groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results The 163 patients with WD had varying severities of liver disease phenotypes,among whom 121(74.23%)were diagnosed with chronic liver disease,36(22.09%)were diagnosed with decompensated cirrhosis,and 6(3.68%)were diagnosed with fulminant WD,and in addition,there were 5 patients(2 with chronic liver disease and 3 with decompensated cirrhosis)with neurological abnormalities.For the 163 patients with WD,R778L mutation(with an allele frequency of 28.2%)was the most common mutation in the ATP7B gene,followed by P992L mutation(with an allele frequency of 12.6%),and truncation mutation showed an allele frequency of 11.0%.There was no significant difference in the distribution of the three mutations across different liver disease phenotypes(P>0.05).The R778L mutation group had a significantly lower level of ceruloplasmin(CP)than the non-R778L mutation group[0.04(0.02-0.08)g/L vs 0.08(0.03-0.13)g/L,Z=-2.889,P=0.004].Compared with the non-P992L mutation group,the P992L mutation group had significantly higher levels of alanine aminotransferase[135.0(80.5-237.0)U/L vs 80.5(36.0-173.3)U/L,Z=2.684,P=0.007]and aspartate aminotransferase[121.4(77.0-195.0)U/L vs 84.0(39.0-123.3)U/L,Z=3.388,P<0.001].Compared with the non-truncation mutation group,the truncation mutation group had significantly lower levels of CP[0.03(0.02-0.08)g/L vs 0.06(0.03-0.11)g/L,Z=-3.136,P=0.002]and serum copper[3.20(2.15-5.00)mg/L vs 4.20(2.60-7.50)mg/L,Z=-2.296,P=0.025].Conclusion R778L mutation,P992L mutation and truncation mutation are not associated with liver disease phenotype in WD patients;however,R778L mutation is associated with a lower level of CP,P992L mutation is associated with higher levels of ALT and AST,and truncation mutation is associated with lower levels of CP and serum copper.