Objective:To investigate effect of acacetin on alveolar epithelial cell damage caused by Streptococcus pneumoniae(SP)infection by regulating sirtuin 1(Sirt1)-mediated 5'-AMP activated protein kinase(AMPK)/nuclear factor erythroid-2 related factor 2(Nrf2)signaling pathway.Methods:Alveolar epithelial cells A549 cultured in vitro were infected with SP to establish a cell damage model.After treatment with acacetin at final concentrations of 0,5,25,50,100,150,200 μmol/L,CCK-8 was performed to detect cell viability of each treatment group and optimal concentration of acacetin was screened.A549 cells cultured in vitro were ran-domly separated into five groups:control group,model group,acacetin(150 μmol/L)group,EX527(Sirt1 inhibitor,40 μmol/L)group,acacetin(150 μmol/L)+EX527(40 μmol/L)group,control group was not treated,other groups were infected with SP to establish a cell damage model,and then treated with 150 μmol/L acacetin and 40 μmol/L EX527,CCK-8 and flow cytometry were performed to measure cell viability and apoptosis rate in each group;kits were performed to measure levels of reactive oxygen species(ROS),superoxide dismutase(SOD),malondialdehyde(MDA),lactate dehydrogenase(LDH)and IL-10,IL-1β,TNF-α levels of cells in each group;Western blot was performed to measure proliferation-related proteins Ki-67,proliferating cell nuclear antigen(PCNA),apoptosis-related proteins caspase-9,Bax,Sirt1 and AMPK/Nrf2 signaling pathway proteins p-AMPK/AMPK,Nrf2 expres-sions of cells in each group.Results:Model group had decreased A549 cell viability,SOD and IL-10 levels,p-AMPK/AMPK,Sirt1,Nrf2,Ki-67 and PCNA protein expressions(P<0.05),and increased apoptosis rate,MDA,LDH,ROS,IL-1β and TNF-α levels than control group(P<0.05).Compared with model group and acacetin+EX527 group,acacetin group had increased A549 cell viability,SOD and IL-10 levels,p-AMPK/AMPK,Sirt1,Nrf2,Ki-67 and PCNA protein expressions(P<0.05),and decreased apoptosis rate,MDA,LDH,ROS,IL-1β and TNF-α levels(P<0.05);EX527 group had decreased A549 cell viability,SOD and IL-10 levels,p-AMPK/AMPK,Sirt1,Nrf2,Ki-67 and PCNA protein expressions(P<0.05),and increased apoptosis rate,MDA,LDH,ROS,IL-1β and TNF-α levels(P<0.05).Conclusion:Acnestin can activate AMPK/Nrf2 signaling by up-regulating Sirt1 expression,thereby promoting secretion of anti-inflammatory factors,reducing production of ROS and pro-inflammatory factors,reducing inflammation and oxidative stress,and finally alleviating neuronal damage.

Objective To explore the mechanism by which Sestrin2(SESN2)regulates autophagy activity of chondrocytes by mediating mammalian rapamycin target protein complex 1(mTORC1)signaling pathway.Methods The normal chondrocytes were treated with interleukin-1 β(IL-1β)to establish an osteoarthritis(OA)chondrocyte model,which was divided into the control group and the IL-1 β-treated group.Real-time quantitative PCR(qPCR)and Western blot were used to detect the expression levels of matrix metalloproteinase 13(MMP13),type Ⅱ collagen(COL2A1)and SESN2 in the two groups.The cell models of the chondrocyte overexpression SESN2 group and knockdown SESN2 group were obtained via cell transfection technology,and the expression levels of SESN2 in each group were detected by qPCR while those of SESN2,MMP13,COL2A1,mTORC1 pathway-related proteins and autophagy-related proteins in each group were detected by Western blot.The effects of SESN2 on cell proliferation and migration were detected by CCK-8 and cell scratch assay.Results(1)The expression level of MMP13 in the IL-1 β-treated group was significantly up-regulated,while the expression levels of COL2A1 and SESN2 were significantly decreased.(2)Compared with the control group,the expressions of p-mTORC1,ribosomal protein S6 kinase 1(S6K1),and MMP13 protein in OA chondrocytes in the overexpression group were significantly down-regulated,while the expressions of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)and chondroprotective gene COL2A1 were significantly increased,and the expression level of Beclin-1 and the ratio of microtubule associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)/(LC3-Ⅰ)were increased.Meanwhile,overexpression of SESN2 could up-regulate the proliferation and migration of chondrocytes,but the results were opposite after knockdown of SESN2.Conclusion SESN2 can enhance autophagy,proliferation and migration of chondrocytes by inhibiting mTORC1 pathway,which has provided data for revealing the pathogenesis of OA and exploring new therapeutic methods.

Objective:To compare the predictive value of parameters extracted from circular region-of-interest (ROI) with whole-liver histogram on gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced T 1 map for postoperative liver failure in patients with liver focal lesions. Methods:The data of patients who underwent Gd-EOB-DTPA-enhanced MRI for focal liver lesions in Zhongshan Hospital, Fudan University from March 2016 to March 2018 were analyzed retrospectively. Forty patients were enrolled, including 30 males and 10 females, aged (56.6±12.1) years. According to the occurrence of postoperative liver failure, forty patients were divided into liver failure group ( n=14) and control group ( n=26). The parameters extracted from circular ROIs and whole liver histogram on T 1 map before Gd-EOB-DTPA enhancement and in hepatobiliary phase (HBP) were compared between the two groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of these parameters in predicting postoperative liver failure. Results:The mean, standard deviation, median and 95% quantile of T 1 HBP in histogram parameters of liver failure group were significantly higher than those of control group (all P<0.05). The three parameters extracted from circular ROIs were not effective in predicting liver failure after hepatectomy (all P>0.05). Among all the liver histogram parameters, the area under the ROC curve of the 95% quantile before T 1 enhancement for predicting postoperative liver failure was 0.702 (95% CI: 0.523-0.881), the standard deviation of T 1 HBP was 0.739 (95% CI: 0.568-0.910), and the 95% quantile of T 1 HBP was 0.721 (95% CI: 0.540-0.903). The predictive efficacy were good (all P<0.05). Among them, the predictive performance of T 1 HBP standard deviation was the best, the area under the ROC curve was 0.739, the sensitivity was 85.7%, the specificity was 57.7%, and the best threshold was 54.8 ms. Conclusions:When Gd-EOB-DTPA enhanced T 1 mapping is used to predict postoperative liver failure in patients with focal liver lesions, the whole-liver histogram analysis is superior to the conventional circular ROI-based statistical method.

Objective:To explore the relationship between 18F-fibroblast activation protein inhibitor (FAPI)-42 SUV max of primary gastric cancer and clinicopathological factors of patients. Methods:Fifty-one patients (31males, 20 females, age: 51(47, 65) years) with gastric cancer who underwent 18F-FAPI-42 PET/CT before surgical resection in Nanfang Hospital, Southern Medical University from February 2022 to January 2023 were analyzed retrospectively. The clinicopathological factors that might affect tumor SUV max (including gender, age, tumor location, pathological type, histological grade, Lauren classification, vascular and(or) neural invasion, programmed cell death-ligand 1 (PD-L1) expression, pathologic(p)T stage, pN stage and pTNM stage) were evaluated by the univariate analysis (Mann-Whitney U test or Kruskal-Wallis rank sum test) and multivariate analysis (multiple linear regression analysis). Results:The sensitivity of 18F-FAPI-42 PET/CT in the diagnosis of patients with primary gastric cancer was 82.35% (42/51). The diagnostic sensitivities for early gastric cancer (T1) and locally advanced gastric cancer (T2-T4) were 59.09%(13/22) and 100%(29/29), respectively. The SUV max of primary lesion was 4.90(1.71, 12.51). The univariate analysis showed that SUV max of primary gastric cancer was related to tumor location ( z=-2.00, P=0.046), pT stage ( H=36.94, P<0.001), pN stage ( z=-3.89, P<0.001), pTNM stage ( H=31.49, P<0.001) and vascular and(or) nerve invasion ( z=-5.22, P<0.001), but not related to pathological type, histological grade, Lauren typing, and PD-L1 expression ( z values: from -1.78 to -0.09, all P>0.05). pT stage was found to be a significant independent factor for SUV max in primary gastric lesion by multivariate analysis ( t=2.52, P=0.015). Conclusions:The 18F-FAPI-42 SUV max of primary tumor was related to tumor location, pT stage, pN stage, pTNM stage, and vascular and(or) nerve invasion; pT stage is an independent factor affecting tumor SUV max. The ability of 18F-FAPI-42 PET/CT to detect gastric cancer is mainly affected by pT stage.

Objective:To analyze the mediating effects of emotional changes in self-management interventions on the relationship between behavioral management and quality of life in elderly patients with type 2 diabetes and therefore to provide a reference for improving the emotional status of elderly diabetes patients and future community-based self-management interventions.Methods:From 2016 to 2020, a total of 69 self-management groups were formed in Hangzhou, each consisting of 10-15 patients with type 2 diabetes.Based on the construction of a medical consortium and family doctors signing up to provide services, intervention teams were established to conduct a series of group self-management activities for each group.Surveys via questionnaires were conducted before and after the intervention, as well as 6 months after the intervention, to collect patient data on demographics, disease status, emotions, quality of life, and self-management behaviors.The intervention effects were evaluated, and the correlations between emotional changes, self-management behaviors, and changes in quality of life were analyzed.Bootstrap analysis was used to test the mediating effects.Results:A total of 707 elderly diabetes patients were included.There were statistically significant differences in the scores of the Self-Rating Anxiety Scale(SAS), the Self-Rating Depression Scale(SDS), physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health, physical component summary, mental component summary, the dietary control dimension of the type 2 diabetes self-care scale(2-DSCS), regular exercise, medication adherence, blood glucose monitoring, foot care, the dimension of prevention and management of hyperglycemia and hypoglycemia, and the total score of 2-DSCS( P<0.05 for all).Compared with pre-intervention, changes in SAS, SDS, physical component summary and mental component summary scores were all correlated with each dimension of 2-DSCS right after intervention and 6 months after intervention( r=-0.336-0.333, P<0.05), with the exception of changes in the blood glucose monitoring dimension score and changes in the emotional status score.The direct effect of self-management behavior on the quality of life in elderly patients with type 2 diabetes was 0.159, and the indirect effect through emotions was 0.229, with the mediating effect accounting for 59.02% of the total effect. Conclusions:Community-based group self-management activities can effectively improve the emotions and management behaviors of elderly diabetes patients and enhance their quality of life, Emotional changes play a certain mediating role between self-management behaviors and improvement in quality of life.

A new variant of concern for SARS-CoV-2,Omicron(B.1.1.529),was designated by the World Health Organization on November 26,2021.This study analyzed the viral genome sequenc-ing data of 108 samples collected from patients infected with Omicron.First,we found that the enrichment efficiency of viral nucleic acids was reduced due to mutations in the region where the primers anneal to.Second,the Omicron variant possesses an excessive number of mutations compared to other variants circulating at the same time(median:62 vs.45),especially in the Spike gene.Mutations in the Spike gene confer alterations in 32 amino acid residues,more than those observed in other SARS-CoV-2 variants.Moreover,a large number of nonsynonymous mutations occur in the codons for the amino acid residues located on the surface of the Spike protein,which could potentially affect the replication,infectivity,and antigenicity of SARS-CoV-2.Third,there are 53 mutations between the Omicron variant and its closest sequences available in public databases.Many of these mutations were rarely observed in public databases and had a low muta-tion rate.In addition,the linkage disequilibrium between these mutations was low,with a limited number of mutations concurrently observed in the same genome,suggesting that the Omicron vari-ant would be in a different evolutionary branch from the currently prevalent variants.To improve our ability to detect and track the source of new variants rapidly,it is imperative to further strengthen genomic surveillance and data sharing globally in a timely manner.

0bjective To construct the program of diet for adults with crohn′s disease. Methods Based on evidence, two rounds of consultation with experts using Delphi method were conducted to construct the program of diet for adults with crohn′s disease. Results The diet program consisted of 5 first-level entries,12 second-1evel entries and 33 third-level entries.The response rate of both rounds' questionnaire were 100%;the authority coefficients were 0.808 and 0.811,respectively;the coordination coefficients ranged from 0.149 to 0.212. Conclusions The Evidence-based diet program for adult with Crohn′s disease was reliable, the experts who participated were representative, had consistent opinions on items of each level for the program of diet for adults with crohn′s disease. Experts also had high levels of enthusiasm and authority, and could provide some degree guidance for diet nursing.

OBJECTIVE: The purpose of this study was to prospectively investigate the value of the myocardial extracellular volume fraction (ECV) in predicting myocardial functional outcome after revascularization of coronary chronic total occlusion (CTO). MATERIALS AND METHODS: Thirty patients with CTO underwent cardiovascular magnetic resonance (CMR) before and 6 months after revascularization. Three baseline markers of functional outcome were evaluated in the dysfunctional segments assigned to the CTO vessels: ECV, transmural extent of infarction (TEI), and unenhanced rim thickness (RIM). At the global level, the ECV values of the whole myocardium with and without a hyperenhanced region (global and remote ECV) were respectively measured. RESULTS: In per-segment analysis, ECV was superior to TEI and RIM in predicting functional recovery (area under receiver operating characteristic curve [AUC]: 0.86 vs. 0.75 and 0.73, all p values < 0.010), and it emerged as the only independent predictor of regional functional outcome (odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.77–0.89; p < 0.001) independent of collateral circulation. In per-patient analysis, global baseline ECV was indicative of ejection fraction (EF) at the follow-up examination (β = −0.61, p < 0.001) and changes in EF (β = −0.57, p = 0.001) in multivariate regression analysis. A patient with global baseline ECV less than 30.0% (AUC, 0.93; sensitivity 94%, specificity 80%) was more likely to demonstrate significant EF improvement (OR: 0.38; 95% CI: 0.17–0.85; p = 0.019). CONCLUSION: Extracellular volume fraction obtained by CMR may provide incremental value for the prediction of functional recovery both at the segmental and global levels in CTO patients, and may facilitate the identification of patients who can benefit from revascularization.
Collateral Circulation ; Coronary Vessels* ; Follow-Up Studies ; Humans ; Infarction ; Magnetic Resonance Imaging* ; Myocardial Infarction ; Myocardial Ischemia ; Myocardium ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity

Objective To investigate the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the staging of chronic kidney disease(CKD).Methods From May 2016 to April 2017,seventy-two patients diagnosed as CKD according to the criteria of clinical diagnostic and 20 healthy volunteers (control group) underwent routine MRI and IVIM-DWI ( 8 b values, 0 to 800 s/mm2).CKD patients were divided into two groups based on their estimated glomerular filtration rate (eGFR): mild CKD group(45 cases,eGFR≥60 ml·min-1·1.73m-2)and moderate to severe CKD group(27 cases,eGFR<60 ml·min-1·1.73 m-2).The ADC,true diffusion coefficient(D),pseudo-diffusion coefficient(D*),perfusion fraction (f) were measured on both cortex and medulla. The paired-samples t test was used to compare the cortico-medullary difference of the ADC,D,D*and f values in three groups.Differences of the ADC,D, D*and f values among three groups were compared using the one-way analysis of variance (ANOVA). Correlations between eGFR and the IVIM-DWI parameters in CKD were evaluated by using Pearson correlation analysis. ROC was performed to evaluate the diagnostic efficiency of using IVIM-DWI parameters to distinguish CKD with moderate to severe renal impairment from mild renal impairment, as well as distinguish CKD with mild renal impairment from healthy volunteers.Results The cortical ADC,D, D*and f values were significantly higher than that in the medulla in healthy volunteers(all P<0.05). The cortical ADC,D*and f values were significantly higher than that in the medulla in mild CKD group(all P<0.05). The cortical ADC,D and f values were significantly higher than that in the medulla in moderate to severe CKD group (all P<0.05). The ADC,D,D*and f values of cortex and medulla showed significantly differences among three groups(all P<0.05).In CKD patients,no significant correlation was found between medullary D*,f values and eGFR, there was a significant positive correlation between eGFR and cortical ADC,D,D*and f values(r=0.475,0.362,0.625,0.276;all P<0.05),as well as between eGFR and medullary ADC,D values(r=0.427,0.615;P<0.05). The results of the ROC analysis for distinguishing the mild CKD group from the moderate to severe CKD group revealed that the cortical D*value had the highest area under the ROC curve (AUC=0.965), cortical f value showed high sensitivity(92.6%) to distinguish CKD with different degree of renal impairment, with the threshold of 32.99%, and cortical D*value showed high specificity(97.8%)with the threshold of 17.07×10-3mm2/s;the results of the ROC analysis for distinguishing the mild CKD group from healthy volunteers revealed that the cortical D*value had the highest AUC(0.885), medullary ADC value showed high sensitivity (82.2%) to distinguish mild CKD group from healthy volunteers,with the threshold of 1.83×10-3mm2/s,and medullary f value showed high specificity(100.0%)with the threshold of 21.70%,as well as medullary D value showed high specificity(100.0%)with the threshold of 1.75× 10-3mm2/s.Conclusion IVIM-DWI may be useful for CKD early diagnosis and assessing renal function.

Objective To explore the correlations between intravoxel incoherent motion (IVIM) parameters measured at different time points and histopathological markers in an orthotopic xenograft hepatocellular carcinoma (HCC) nude mice model. Methods A total of 40 HCC orthotopic bearing mouse models were established. When they grew to 21 days, 10 HCC-bearing mice were randomly selected as the baseline group (Group A) by a numeric table method. Then the rest mice were randomly selected on the 28th day, 35th day, and 42nd day of the growth by using the same method, 10 each for B, C, and D groups, respectively. All mice underwent MR IVIM study and apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion fraction (f) were measured. After the MRI scanning, the tumors were removed for pathological examination. The necrosis score (NF), tumor size and microvessel density (MVD) were calculated. The IVIM parameters were compared among these 4 groups by Kruskal-Wallis H test and the correlations between these IVIM parameters and histological features were studied with Spearman rank correlation test. Results One tumor in each of C and D groups was excluded because f values of IVIM were close to zero. There were significant differences found in ADC and D among all the 4 groups (P＜0.05). However, no difference was found in D*and f (P＞0.05). Compared with the baseline (group A), ADC decreased significantly at 7 and 14 days, whilst D decreased significantly at 7 days. The differences in tumor size, MVD and NF between the 4 groups were statistically significant. Compared with the baseline, the tumor size and NF significantly increased at 7, 14 and 21 days, and MVD increased at 14 and 21 days. Significantly positive correlations were demonstrated between ADC and MVD, NF (r=0.461 and 0.442, P＜0.05), between D and MVD, NF (r=0.568 and 0.519, P＜0.05) after exclusion of the data from the baseline. The parameter f from all the time points including the baseline was positively correlated with histological MVD and NF (r=0.590 and 0.458, P＜0.05). Conclusion IVIM parameters may reflect the intratumoral vascularity, tumor cell proliferation and necrosis of HCC, and they are correlated with the pathological indicators.