With the advent of an aging society,Alzheimer's disease(AD)has gradually become a major ailment affecting the elderly.AD is a neurodegenerative disorder associated with cognitive impairments.In AD patients,brain network connections are disrupted,and their topological properties are also affected,leading to the disintegration of anatomical and functional connections.Anatomical connections can be tracked and evaluated using structural magnetic imaging(MRI)and diffusion tensor imaging(DTI),while functional connections are detected through functional MRI to assess their connectivity status.This review incorporates the findings of previous scholars and summarizes the current research of AD.It mainly discusses the imaging characteristics of large-scale brain network changes in AD patients,so as to provide researchers with scientific and objective imaging markers for AD prediction and early diagnosis,as well as future research.

Objective:To construct checklist teaching management combined with a bidirectional evaluation system in clinical nursing teaching.Methods:A total of 120 nursing students who interned from March to July 2023 and 30 qualified clinical nursing teachers were selected to conduct a questionnaire survey. The data and information were collated and analyzed using qualitative and quantitative research. Based on the results of the questionnaire survey, checklist teaching management combined with the bidirectional evaluation system and evaluation indicators were constructed in line with the requirements of clinical nursing teaching. Reliability and validity tests were conducted using SPSS 27.0. Teaching effectiveness was analyzed through difference analysis. Principal component analysis was used to investigate the evaluation indicators identified in qualitative research and to determine the weights of these indicators.Results:The clinical nursing teaching quality bidirectional evaluation indicators showed a KMO value of 0.884 and a Cronbach's Alpha value of 0.940, indicating high reliability and validity of these indicators and the evaluation system. The principal component analysis identified seven evaluation indicators, i.e., teaching attitude, teaching ability, teaching responsibility, cooperative consciousness, learning ability, operating ability, and professional quality, and their loading values were all higher than 0.5. The paired sample rank sum test showed significant differences in teaching quality and all dimensions of bidirectional evaluation of clinical nursing teaching quality under checklist teaching management before and after teaching. The mean rank after teaching (194.86) was higher than that before teaching (106.14). These results indicated that the intervention of checklist teaching management combined with the bidirectional evaluation system significantly improved the bidirectional evaluation of clinical nursing teaching quality.Conclusions:The combination of checklist teaching management with the bidirectional evaluation system is effective in promoting the clinical nursing education and can enhance the effectiveness of clinical nursing teaching.

Objective To investigate the protective effect of apigenin on renal tubular epithelial cells(HK-2)induced by hyperglycemia and its potential mechanism.Methods HK-2 cells were incubated with d-glucose to establish an in vitro diabetic nephropathy model.Cell viability,apoptosis and oxidative stress were assessed.The mRNA levels of nuclear factor erythroid-2 related factor 2(Nrf2),heme oxygenase-1(HO-1)and epoxy chloropropane Kelch sample related protein-1(Keap1)were measured by quantitative real-time-PCR(q-PCR).Western blot analysis was performed to measure the protein expression of Nrf2.Results In HK-2 cells,high glucose decreased cell viability in a concentration-and time-dependent manner.Apigenin improved the viability of HK-2 cells under high glucose stress,reduced apoptosis and proinflammatory cytokine production,and inhibited the oxidative stress.Apigenin increased mRNA expression of Nrf2 and HO-1,increased expression of Nrf2 protein and reduced the mRNA level of Keap1.Inhibition of Nrf2 using small interfering RNA(siRNA)abolished the protective effects of apigenin on HK-2 cells under high glucose stress.Conclusion Apigenin treatment can alleviate the damage of HK-2 cells under high glucose stress,and exert the anti-oxidation and anti-inflammation effects through Keap1-Nrf2-ARE pathway.

Objective    To assess the specific clinicopathological characteristics as well as prognostic value of prognostic significance of spread through air spaces (STAS) in lung adenocarcinoma. Methods    We systematically searched the databases of PubMed, EMbase and Web of Science databases from their date of inception to March 2019. The quality of the included literature was assessed by the Newcastle-Ottawa scale (NOS). The NOS of the study higher than 6 points was considered as high quality. Software of Stata 12.0 was used for meta-analysis. Results    Twenty retrospective cohort studies involved with totally 6 225 patients were included. Quality of included studies was high with NOS score equal or higher than 6 points. STAS was associated with male sex, ever smoking history, abnormal carcino-embryonic antigen (CEA) level, air bronchogram negative, anaplasticlymphoma kinase (ALK) arrangement positive, epidermal growth factor receptor (EGFR) mutation positive, advanced pathological tumor stage and more invasive pathological adenocarcinoma subtypes. The presence of STAS indicated significantly poor recurrence free survival (RFS) (HR=1.960, 95%CI 1.718-2.237, P<0.001) as well as poor overall survival (OS) (HR=1.891, 95%CI 1.389-2.574, P<0.001). Further subgroup analyses showed that exhibiting tumor size including diameter less than 2 cm (HR=2.344, 95%CI 1.703-3.225,  P<0.001) and diameter over 2 cm (HR=2.571, 95%CI 1.559-4.238, P<0.001), resection type including lobectomy (HR=1.636, 95%CI 1.258-2.127, P<0.001) and sublobar resection (HR=3.549, 95%CI 2.092-6.021, P<0.001) in stageⅠ adenocarcinoma suggested that STAS had a bad effect on RFS. Conclusion    Presence of STAS is associated with more aggressive clinicopathological features and independently associated with worse RFS and OS in lung adenocarcinoma. STAS positive has a negative effect on RFS whatever the tumor size (including the diameter<2 cm or >2 cm) and resection types in stageⅠ adenocarcinoma.

Objective To evaluate the effect of berberine on fatty liver ischemia-repeffusion (I/R) injury and the relationship with endoplasmic reticulum stress in liver tissues.Methods Thirty-two male Wistar rats,aged 4 weeks,weighing 100-150 g,were divided into 4 groups (n=8 each) using a random number table method:control group (group C),fatty liver group (group FL),I/R group and berberine group (group BBR).Rats were fed a normal fat diet for 12 weeks,normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and rats only underwent simple laparotomy in group C.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,and the other treatments were similar to those previously described in group C.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and then the model of liver I/R injury was established in group I/R.Rats were fed a high-fat diet (45％ energy originating from fat) for 12 weeks,berberine solution (300 mg/kg) 3.5 ml was given intragastrically for 4 weeks starting from 9th week,and then the model of liver I/R injury was established in group BBR.Hepatic ischemia was induced by clamping the portal vein,hepatic artery,right gastric vein,and supra-and inferior-hepatic vena cava to perform cold perfusion with 4 ℃ lactated Ringer's solution lasting for 30 min,followed by reperfusion.The serum triglyceride (TG) concentrations were determined after 4,8 and 12 weeks of diet.Blood samples were collected at 6 h of reperfusion for measurement of serum aspartate transminase (AST) and alanine transaminase (ALT) concentrations.Livers were removed after blood sampling at 6 h of reperfusion and liver tissues were obtained and stained with oil red O and haematoxylin and eosin for examination of pathological changes and for determination of the expression of Bip,CCAAT/enhancer-binding protein homologous protein (CHOP),protein kinase RNA-like endoplasmic reticulum kinase (PERK) and phosphorylated PERK (p-PERK) (by Western blot).p-PERK/PERK ratio was calculated.Results Compared with group C,the serum TG,ALT and AST concentrations were significantly increased,the expression of Bip and CHOP was up-regulated,p-PERK/PERK ratio was increased (P＜0.05),lipid deposition was increased,and liver steatosis was found in group FL.Compared with group FL,the serum AST and ALT concentrations were significantly increased,the expression of Bip and CHOP was up-regulated,pPERK/PERK ratio was increased (P＜0.05),and the pathological changes of liver tissues were accentuated in group I/R.Compared with group I/R,the serum TG,ALT and AST concentrations were significantly decreased,the expression of Bip and CHOP was down-regulated,p-PERK/PERK ratio was decreased (P＜ 0.05),lipid deposition was reduced,and the pathological changes of liver tissues were significantly attenuated in group BBR.Conclusion Berberine can ameliorate fatty liver I/R injury,and the mechanism may be related to inhibiting endoplasmic reticulum stress in liver tissues of rats.

Objective To explore the effect of berberine (BBR) on steatotic liver ischemia reperfusion injury and analyze the role of endoplasmic reticulum stress and autophagy .Methods Thirty-four Wistar rats were fed with a high-fat diet for 12 weeks and 2 rats were randomly selected after 8 weeks to observe pathological changes and confirm the model of steatotic liver successfully .Then before opening and closing abdominal cavity ,32 rats were divided into I/R group (normal saline was intragastrically 4 weeks before performing cold I/R treatment) ,BBR group (normal saline was replaced by BBR ,BBR was intragastrically at a dose of 300 mg·kg-1 ·d-1 weeks and others were the same as I/R group) and TG group (TG was intraperitoneally at a dose of 0 .2 mg·kg-124h pre-operation and others were the same as BBR group ) .Then the rats were sacrificed at 6h post-reperfusion .Blood samples were collected from inferior vena cava and hepatic tissues harvested .The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected ,histopathologic changes observed by Hematoxylin & Eosin (HE) staining ,oxidative stress and inflammation determined by ELISA kit and the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 detected by Western blot .Results As compared with Sham group ,the serum levels of ALT and AST were significantly higher in I/R ,BBR and TG groups (P < 0 .05) .And hepatic histological changes were severe and oxidative stress increased in parallel with the enhancement of pro-inflammation (P< 0 .05) .In BBR group ,the level of hepatic enzymes declined ,liver injury was milder ,oxidative stress decreased and pro-inflammation was lesser compared with I/R and TG groups (P< 0 .05) .Additionally ,as compared with sham group ,the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 were up-regulated in I/R and BBR groups (P < 0 .05) .TG group increased the levels of LC3 ,Beclin-1 and p62 (P< 0 .05) .Interestingly ,compared with I/R group ,BBR pretreatment down-regulated the expressions of p-PERK ,CHOP ,Bip ,LC3 ,Beclin-1 and p62 (P< 0 .05) .TG group had the higher expressions of LC3 ,Beclin-1 and p62 than those of BBR group (P< 0 .05) .Conclusions BBR pretreatment can protect steatotic liver ischemia reperfusion injury .And the mechanisms may be attributed to the inhibitions of endoplasmic reticulum stress and autophagy .

Objective To study the risk factors and prognosis of post-transplant diabetes mellitus (PTDM) in recipients with steatotic donor livers.Method The clinical data of 182 patients who underwent liver transplantation from donors with liver steatosis in Tianjin First Central Hospital from June 2002 to December 2010 were retrospectively analyzed.There were sixteen patients with PTDM and one hundred sixtysix without PTDM.The clinical data of these patients were compared and the risk factors were evaluated by COX regression analysis.The 1-,3-,5-year cumulative survival rates were analyzed after liver transplantation.Result The variables which included sex,pretransplant serum creatinine level,model for end-stage liver disease (MELD) score,intraoperative red blood cell transfusion,and post-transplant biliary complications were significantly different between the two groups.Multivariate Cox regression analysis showed that living-donor,pretransplant fasting blood glucose and post-transplant biliary complications could affect the survival time of patients in PTDM group.The 1-,3-and 5-year cumulative survival rates in the PTDM group were 81.3％,68.8％ and 62.5％,which were significantly lower than those in the non-PTDM group (95.2％,86.1％ and 80.7％ respectively,P ＜ 0.05).Conclusions Living-donation,pretransplant fasting blood glucose and post-transplant biliary complications had a worse prognosis in the PTDM group.A comparatively better long-term survival after liver transplantation can be achieved by reducing the risk factors and the occurrence of PTDM.

Objective: To analyze the therapeutic effect on HBeAg-negative chronic hepatitis B patients treated with Peg-IFNα-2a combined with NAs to obtain the influencing factors for predicting HBsAg clearance. Methods: A retrospective study was conducted to investigate the effect of pegylated interferon alpha-2a combined with nucleoside analogues (lamivudine/adefovir dipivoxil) on HBeAg-negative chronic hepatitis B. The treatment course was 96 weeks. Patients were followed up 120 weeks after the treatment. HBsAg clearance at 120 weeks was taken as the objective of the study. Logistic regression and receiver operating characteristic curve analysis screened the related factors affecting HBsAg clearance. χ ² test was used to compare count data. Results: 111 patients were treated with pegylated interferon alpha-2a combined with nucleoside analogues, and 107 patients completed the scheduled course of treatment and follow-up. HBsAg clearance rate at120 week was 29.0% (31/107). The influencing factors for analysis were: (1) gender had no effect on HBsAg clearance rate; age and baseline levels of HBV DNA and alanine aminotransferase had no significant effect on HBsAg clearance; low baseline level of HBsAg (< 3.023 lgIU/ml) was beneficial to HBsAg clearance. The area under the working characteristic curve of the subjects was 0.746, the positive predictive value was 44.4%, and the negative predictive value was 86.8%. (2) HBsAg quantification or decline in 24 weeks and 48 weeks of treatment had a good predictive effect on HBsAg clearance, and the 48 weeks predicted value was higher than 24 weeks. When the HBsAg quantification was≤2.070 lgIU/ml at 48 weeks, the area under the receiver operating characteristic curve was 0.931, the positive predictive value was 52.8%, and the negative predictive value was 94.4%. When HBsAg decreased from baseline to≥0.991 lgIU/ml, the area under the receiver operating characteristic curve was 0.888, the positive predictive value was 50.8%, and the negative predictive value was 97.9%. (3) The analysis of HBsAg subgroup levels at 48 weeks suggested that the "interval analysis" can forecast HBsAg clearance more exactly than "nodal analysis" .The final HBsAg clearance rate of 100 IU/ml < HBsAg≤1 000 IU/ml, 10 IU/ml < HBsAg≤100 IU/ml and HBsAg≤10 IU/ml groups reached 6.7%, 31.8% and 67.7%, respectively. (4) The ALT abnormal group in the course of treatment obtained a higher HBsAg clearance rate (48.0%, 12/25). Conclusion 96-weeks long-term treatment with pegylated interferon-alpha -alpha-2a combined with nucleoside analogues for HBeAg-negative chronic hepatitis B has a good predictive value for HBsAg clearance at baseline and during treatment. The "interval level" of HBsAg at 48-weeks is more accurate in predicting HBsAg clearance, suggesting that HBeAg-negative chronic hepatitis B patients with low HBsAg levels at 48-weeks are the advantageous populations with HBsAg clearance. These patients are worthy of prolonged treatment to pursue "clinical cure".

Fucoidan has been reported to exhibit various beneficial activities ranging from to antivirus and anticancer properties. However, little information is available about the effects of fucoidan on cerebral ischemia-reperfusion injury (IRI). Our study aimed to explore the effects of fucoidan on cerebral IRI, as well as the underlying mechanisms. Sprague-Dawley (SD) rats were randomly subjected to four groups: Sham, IRI+saline (IRI+S), IRI+80 mg/kg fucoidan (IRI+F80), and IRI+160 mg/kg fucoidan (IRI+F160). Fucoidan (80 mg/kg or 160 mg/kg) was intraperitoneally injected from 7 days before the rats were induced to cerebral IRI model with middle cerebral artery occlusion (MCAO) method. At 24 h after reperfusion, neurological deficits and the total infarct volume were determined. The levels of inflammation-associated cytokines (interleukin (IL)-1β, IL-6, myeloperoxidase (MPO), and tumor necrosis factor (TNF)-α), oxidative stress-related proteins (malondialdehyde (MDA) and superoxide dismutase (SOD)) in the ischemic brain were measured by enzyme-linked immunosorbent assay (ELISA). Besides, the levels of apoptosis-related proteins (p-53, Bax, and B-cell lymphoma (Bcl)-2) and mitogen-activated protein kinase (MAPK) pathway (phosphorylation-extracellular signal-regulated kinase (p-ERK), p-c-Jun N-terminal kinase (JNK), and p-p38) were measured. Results showed that administration of fucoidan significantly reduced the neurological deficits and infarct volume compared to the IRI+S group in a dose-dependent manner. Also, fucoidan statistically decreased the levels of inflammation-associated cytokines, and oxidative stress-related proteins, inhibited apoptosis, and suppressed the MAPK pathway. So, Fucoidan plays a protective role in cerebral IRI might be by inhibition of MAPK pathway.
Animals ; Apoptosis ; Brain ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Infarction, Middle Cerebral Artery ; Interleukin-6 ; Lymphoma, B-Cell ; Methods ; Peroxidase ; Phosphotransferases ; Protein Kinases ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion Injury* ; Superoxide Dismutase ; Tumor Necrosis Factor-alpha