OBJECTIVES: To investigate the role of activating transcription factor 3 (ATF3) in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis (AS) progression. METHODS: Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting. Apolipoprotein E-deficient (ApoE^-/-) mouse models of AS induced by high-fat diet (HFD) feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9 (AAV9) to knock down ATF3 expression. After an additional 5 weeks of HFD feeding, the mice were euthanized for analyzing structural changes of the aortic plaques, and the expression levels of ATF3, inflammatory factors (CD45, CD68, IL-1β, and TNF-α), and NF-κB pathway proteins (P-IKKα/β and P-NF-κB p65) were detected. In the cell experiment, THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF‑κB signaling. RESULTS: In human atherosclerotic plaques, ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE^-/- mice significantly increased aortic plaque volume, upregulated the inflammatory factors, enhanced phosphorylation of the NF‑κB pathway proteins, and increased the expressions of VCAM1, MMP9, and MMP2 in the plaques. In THP-1-derived foam cells, ATF3 silencing caused activation of the NF‑κB pathway, while ATF3 overexpression suppressed the activity of the NF-κB pathway. CONCLUSIONS AS promotes ATF3 expression, and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway, suggesting the potential of ATF3 as a therapeutic target for AS.
Animals ; Activating Transcription Factor 3/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Humans ; Mice ; Plaque, Atherosclerotic/metabolism* ; Inflammation/metabolism* ; Apolipoproteins E ; Atherosclerosis/metabolism* ; Diet, High-Fat

Objective:To compare the consistency of lymphoma multigene detection panels based on next-generation sequencing (NGS) with FISH detection of B-cell lymphoma gene rearrangement.Methods:From January 2019 to May 2023, fusion genes detected by lymphoma-related 413 genes that targeted capture sequencing of 489 B-cell lymphoma tissues embedded in paraffin were collected from Henan Cancer Hospital, and the results were compared with simultaneous FISH detection of four break/fusion genes: BCL2, BCL6, MYC, and CCND1. Consistency was defined as both methods yielding positive or negative results for the same sample. The relationship between fusion mutation abundance in NGS and the positivity rate of cells in FISH was also analyzed.Results:Kappa consistency analysis revealed high consistency between NGS and FISH in detecting the four B-cell lymphoma-related gene rearrangement ( P<0.001 for all) ; however, the detection rates of positive individuals differed for the four genes. Compared with FISH, NGS demonstrated a higher detection rate for BCL2 rearrangement, a lower detection rate for BCL6 and MYC rearrangement, and a similar detection rate for CCND1 rearrangement. No correlation was found between fusion mutation abundance in NGS and the positivity rate of cells in FISH. Conclusions:NGS and FISH detection of B-cell lymphoma gene rearrangement demonstrate overall good consistency. NGS is superior to FISH in detecting BCL2 rearrangement, inferior in detecting MYC rearrangement, and comparable in detecting CCND1 rearrangement.

Objective:To explore the application value of magnifying endoscope and flexible spectral imaging colour enhancement(ME-FICE)combined with small ultrasound probe in the diagnosis of early gastric cancer and precancerous lesions.Methods:A total of 80 patients with suspected gastric cancer who admitted to Wuhan Red Cross Hospital from April 2021 to April 2022 were selected,and the ME-FICE was used to distinguish positive and/or negative lesions,and then,small ultrasound probe with high-frequency were used to explore the depth of the infiltration of the lesions.After the examination,biopsy should be performed on the obvious position of lesion under FICE mode.The endoscopic mucosal resection(EMR),endoscopic submucosal dissection(ESD)or surgical resection were performed on the lesions according to the different intentions of the positive patients.The result of postoperatively pathological examination was the"gold standard"for diagnosis.Kappa consistency test was used to evaluate the consistency of benign and malignant diagnosis,the assessment of infiltration depth under endoscope and the assessment of infiltration depth after surgery between ME-FICE combined with small ultrasound probe and pathological examination.Results:The sensitivity,specificity and accuracy of ME-FICE combined with small ultrasound probe were respectively 90.63%,79.17%and 83.75%for benign and malignant diagnosis,which were at higher levels.The Kappa value of that was 0.887,which had favorable consistency with the result of biopsy for cases.The sensitivity,specificity and accuracy of ME-FICE combined with small ultrasound probe were respectively 66.67%,90.00%and 81.25%for the assessment of infiltration degree,indicating poor sensitivity and higher level of other indicators,with a Kappa value of 0.803,which had favorable consistency with postoperatively pathological results.Conclusion:ME-FICE combined with small ultrasound probe is suitable for the diagnosis of early gastric cancer and precancerous lesions,which can improve the sensitivity and accuracy of disease diagnosis,and more accurately assess the degree of infiltration before surgery,and provide guidance for subsequently surgical selection and treatment.

Objective: To explore the effects of community building environment and sports with fitness APP usage and their interactions on teachers exercise habits in the Yangtze River Delta Region, so as to provide a scientific basis for the development of a sports and health promotion intervention program for teachers. Methods: A total of 2 530 in service teachers from four provinces and cities in the Yangtze River Delta region, namely, Shanghai, Zhejiang, Jiangsu and Anhui Province, were sampled in May-June 2023 by using convenient cluster random sampling method. Self designed questionnaire was used to collect the basic information of the surveyed teachers, Physical Activity Building Environment Evaluation Questionnaire and the Sports with Fitness APP Usage Questionnaire were used to measure the teachers subjective perception of the community building environment and the usage of sports with fitness APP, respectively. Physical Exercise Habituation Scale was used to assess the level of exercise habits. Logistic regression models were applied to analyze the effects of community building environment and sports with fitness APP usage on physical exercise, and the interaction effects were analyzed by using additive and multiplicative models. Results: Among all the teachers surveyed, 658 of them reported good physical exercise habits (26.0%), and differences in the rate of physical activity habit formation by gender, age, years of teaching, as well as subject of teaching were statistically significant ( χ 2=42.94, 39.73, 35.47, 218.23 , P <0.05). Teachers with physical exercise habits had significantly higher community building environment scores and sports and fitness APP use than teachers without exercise habits ( t =12.17,16.54, P <0.05). Adjusting for the confounders of age, gender, years of teaching experience, and subjects taught, multifactorial unconditional Logistic regression analysis showed that the probability of teachers having good physical exercise habits increased by 22% for every 1-point increase in the community building environment score on average ( OR =1.22, 95% CI =1.11-1.40), and the probability of teachers having good physical exercise habits increased by 16% for every 1-point increase in the sports with fitness APP score on average ( OR = 1.16 , 95% CI =1.03-1.31) ( P <0.05). Interaction analyses showed that there was an additive interaction between the effects of community building environment and sports and fitness APP use on teachers physical exercise habits after adjustment, and the 95% CI for RERI , API and SI were 1.17 -1.65, 0.12-0.46 and 1.78-3.33 ( P <0.05), respectively, and there was no multiplicative interaction ( P >0.05). Conclusions The community building environment and the usage of sports & fitness APP show impacts in the formation of teachers physical exercise habits in the Yangtze River Delta region, and there is an interaction effect. Enhancing the construction of smart sports centers around the community can provide a high quality external environment for the physical exercise habits formation.

Objective To mine and analyse the hub genes associated with the prognosis of basal-like breast cancer(BLBC)by bioinformatic methods.Methods We searched the GEO database to obtain an appropriate microarray dataset related to molecular subtyp-ing of breast cancer,and identified modules associated with BLBC by WGCNA.Then,the top 10％differential expressed genes in the module were screened as candidate genes using PPI and cytohubba.The candidate genes were subjected to survival analysis and expression analysis to obtain hub genes.Finally,we explored the correlation between the expressive level of hub genes and immune cell infiltration,chemokines,and immunomodulators by TIMER and TISIDB database.Furthermore,transcription factors(TFs)-hub gene network was constructed.Results A total of 891 genes in black modules related to BLBC were analyzed,and two hub genes,ESPL1 and CCNB2,were identified from the 80differential expressed genes.Two hub genes are associated with BLBC immune cell infiltration,mainly inclu-ding Th2 cells,CD8+T cells,endothelial cells,and tumor-associated fibroblasts.They were also related to chemokines,immunostimu-lators,immunosuppressive factors,and MHC molecules.The upstream transcriptional regulatory network of hub genes showed that 22 transcription factors simultaneously regulate two hub genes.Conclusion ESPL1 and CCNB2 are prognostic markers of BLBC and related to breast tumor immunity.

Objective: To investigate the causal relationship between junior high school students aggressive behavior, physical exercise and academic performance, so as to provide a reference basis for the development of scientific exercise programs. Methods: A longitudinal followup study was conducted on 502 junior high school students over a 12month period from June 2021 to June 2022 using the Buss-Perry Aggressive Questionnaire (BPAQ), Physical Activity Questionnaire for Adolescents (PAQ-A), and test scores as the measurement tools (T1:June 2021, T2:December 2021, T3:June 2022), and a crosslagged model was constructed to measure the relationship between aggression, physical activity and academic performance. Results: At T1, physical exercise had a positive effect on academic performance at T2 (β=0.22) and a negative effect on aggressive behavior at T2 (β=-0.13), aggressive behavior negatively affected academic performance at T2 (β=-0.23), and academic performance had a negative effect on aggressive behavior at T2 (β=-0.09). Physical exercise at T2 had a negative effect on aggressive behavior at T3 (β=-0.05) and a positive effect on academic performance at T3 (β=0.19). Aggressive behavior at T2 negatively influenced academic performance at T3 (β=-0.08). Academic performance at T2 negatively influenced aggressive behavior at T3 (β=-0.06) (P<0.05). The results of crosslagged modeling of junior high school students aggressive behavior, physical exercise and academic performance showed that the model was well fitted (χ2/df=8.80, CFI=0.96, NFI=0.95, RFI=0.87, IFI=0.96, TLI=0.88, RMSEA=0.12). The results of multigroup structural equation modeling showed that the differences between the models and the baseline model (CFI=0.95, TLI=0.86, RMSEA=0.10, 90%CI=0.08-0.11, P<0.01) were not statistically significant in terms of gender (△CFI<0.05, P>0.05). Conclusions Physical exercise negatively predictes aggressive behavior and positively predictes academic performance, and academic performance and aggressive behavior negatively affect each other. A scientific exercise program should be developed to reduce aggression and effectively improve adolescents academic performance.

Background::Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Methods::Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients ( n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group ( n = 56) and a twice or three times per week intravenous epoetin alfa group ( n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion::Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.

Background::Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia.Methods::Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients ( n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group ( n = 56) and a twice or three times per week intravenous epoetin alfa group ( n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis.Conclusion::Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Background::This study was to explore the clinical efficacy and safety of darbepoetin alfa injection replacing epoetin alfa injection (recombinant human erythropoietin injection, rHuEPO) for the treatment of anemia associated with chronic kidney failure in Chinese patients undergoing hemodialysis.Method::This study was a multicenter, randomized, open-label, intergroup parallel control phase III noninferiority trial from April 19, 2013 to September 9, 2014 at 25 sites. In this study, the members of the darbepoetin alfa group underwent intravenous administration once per week or once every two weeks. The members of the control drug epoetin alfa group underwent intravenous administration two or three times per week. All subjects underwent epoetin alfa administration during the 8-week baseline period. After that, subjects were randomly assigned to the darbepoetin alfa group or epoetin alfa group. The noninferiority in the changes of the average Hb concentrations from the baseline to the end of the evaluation period (noninferiority threshold: -1.0 g/dl) was tested between the two treatments. The time-dependent hemoglobin (Hb) concentration and the maintenance rate of the target Hb concentration (the proportion of subjects with Hb concentrations between 10.0 and 12.0 g/dl) were also evaluated. Iron metabolism, including changes in the serum iron, total iron-binding capacity, ferritin, transferrin saturation, and comparisons of the dose adjustments between the two groups during the treatment period were analyzed further. Adverse events (AEs) were also observed and compared, and the safety was analyzed between the two treatment groups. The conversion rate switching from epoetin alfa to darbepoetin alfa was also discussed. SAS ? software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. Results::Four hundred and sixty-six patients were enrolled in this study, and ultimately 384 cases were analyzed for safety, including 267 cases in the darbepoetin alfa group and 117 cases in the epoetin alfa group. There were 211 cases in the per-protocol set, including 152 cases in the darbepoetin alfa group and 59 cases in the epoetin alfa group. The changes in the average Hb concentrations from the baseline to the end of the evaluation period were -0.07 and -0.15 g/dl in the darbepoetin alfa group and epoetin alfa group respectively. The difference between the two groups was 0.08 g/dl (95% confidence interval [CI]: -0.22 to 0.39), and the lower limit of the 95% CI was -0.22 > -1.0 g/dl. The average Hb concentrations of the two groups were 10.88-11.43 g/dl (darbepoetin alfa) and 10.91-11.38 g/dl (epoetin alfa) during the study period of Weeks 0-28, with the maintenance rates of the target Hb concentration ranging within 71%-87% and 78%-95% in the darbepoetin alfa group and epoetin alfa group respectively. During the period of comparison between the two groups, the incidence of AEs in the darbepoetin alfa group was 61.42%, while in the epoetin alfa group it was 56.41%. All of the adverse events and reactions in the study were those commonly associated with hemodialysis.Conclusion::The overall efficacy and safety of darbepoetin alfa for the treatment of Chinese renal anemia patients undergoing hemodialysis are consistent with those of epoetin alfa.