Objective:To investigate the effects of dictyophora polysaccharides(DIP)on cognitive dysfunction induced by chronic alco-hol exposure in rats.Methods:Sixty male Sprague-Dawley(SD)rats were randomly divided into five groups(n=12):control group(normal saline),DIP group[DIPH,DIP administered by gavage at 300 mg/(kg·d)for 28 consecutive days],alcohol group[EtOH,60%alcohol administered by gavage at 10 mg/(kg·d)for 28 consecutive days],low-dose DIP treatment group[EtOH+DIPL,60%alcohol administered at 10 mg/(kg·d)and DIP administered at 100 mg/(kg·d)by gavage,with an interval of 6 hours between doses,for 28 consecutive days],and high-dose DIP treatment group[EtOH+DIPH,60%alcohol administered at 10 mg/(kg·d)and DIP administered at 300 mg/(kg·d)by gavage,with an interval of 6 hours between doses,for 28 consecutive days].On day 25 of gavage,water maze training was provided for the rats for 4 days.On day 29,a water maze test was performed to determine the memory and learning functions of the rats;HE staining was used to evaluate the edema and inflammation of the liver and brain tissues;presence of inflammatory cells and the expression of myelin basic protein(MBP)in brain tissue were measured using immunohistochemical staining;Western blot was used to measure the expression of 2,2-cyclic nucleotide-3-phosphodiesterase(CNP)in the hippocampal tissue;the structural integrity of the myelin sheath was evaluated using LuxoL fast blue(LFB)staining and transmission electron microscopy.Results:Compared with the control group,the EtOH group showed a significantly increased escape latency,reduced expression of MBP,and decreased density of the myelin sheath.DIP intervention significantly improved cognitive dysfunction in rats,increased the expression of MBP and CNP,and reduced myelin damage.Conclusion:At a dose of 300 mg/kg,DIP may ameliorate cognitive dysfunction induced by chronic alcohol exposure by pro-tecting the structural and functional integrity of myelin sheaths.

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 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 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 investigate the age-related changes of biomechanical properties for humerus, femur and tibia in male rats and their application values in age estimation. Methods According to different weeks of age, 90 healthy male SD rats were divided into 2, 4, 6, 8, 17, 26, 52, 78 and 104-week groups with 10 rats in eachgroup. After the rats were executed by excessive anesthesia, humerus, femur, and tibia were separated and the attached soft tissues were removed. The length of the above-mentioned bones and the diameter of the middle section (compression site) were measured with vernier caliper, and the three-point bending test was conducted with electronic universal material testing machine to detect the ultimate load and displacement under ultimate load. Results There were significant differences in the ultimate load of humerus, femur and tibia among male rats in different age groups (P<0. 05). With the increase of week age, the ultimate loads of the humerus, femur and tibia increased first and then decreased, and reached the peak value in 52-week age group, showing a strong positive correlation with week age before 52 weeks ( r = 0. 884,0. 933,0. 929, P<0. 05). There was no significant difference in humerus and tibia. The displacement of femur under ultimate load was weakly positively correlated with week age (R= 0. 406,P<0. 05). The age prediction accuracy for automatic linear modeling of ultimate load for humerus, femur, tibia and three above-mentioned bones in rats before 52-week age was 78. 2% , 86. 8% , 84. 1% and 88. 3% , respectively. There was a strong positive correlation between the length of humerus, femur and tibia and the ultimate load (R= 0. 904, 0. 897, 0. 814, P<0. 05). The diameters of humerus, femur and tibia were strongly positively correlated with the ultimate load (R = 0. 759, 0. 814 and 0. 745, P<0. 05). Conclusions The ultimate loads of humerus, femur and tibia in male rats increased first and then decreased with age, and were positively correlated with age before 52 weeks, which could be used for age inference. The highest accuracy of age estimation was ultimate loads of three bones, followed by femur. The length/ middle diameter of humerus, femur and tibia were strongly positively correlated with the ultimate load.

Objective:To assess the clinical and imaging features of SMARCB1-deficient sinonasal carcinoma.Methods:Form January 2016 to November 2021, the clinical data and pretreatment imaging findings of 16 cases with pathologically proven SMARCB1-de?cient sinonasal carcinomas were analyzed retrospectively in Beijing Tongren Hospital, Capital Medical University. Immunohistochemistry for SMARCB1 showed loss of the protein in the tumor nuclie. Clinical and imaging features, including tumor location, TNM stage, size, density of CT, bone change, MRI signal intensity, enhancement pattern, type of time-intensity curve (TIC) of dynamic contrast enhanced MRI (DCE-MRI), apparent diffusion coefficient (ADC) value and diffusion weighted imaging (DWI) were evaluated. For 14 cases, correlation of the ADC value and Ki-67 index was subsequently evaluated with Pearson correlation analysis.Results:For the 16 cases SMARCB1-deficient sinonasal carcinomas, clinical stage of T4 was 12 cases and T3 was 4 cases. The location included ethmoid sinus ( n=4), nasal cavity only ( n=1), both nasal cavity and ethmoid ( n=8), ethmoid and maxillary sinus ( n=1), ethmoid and frontal sinus ( n=1), ethmoid and sphenoid sinus ( n=1). The tumor size was (4.5±1.2) cm. Iso-attenuated of CT images was showed in 13 cases and heterogeneous with necrosis was showed in 3 cases. Focal bone erosion was found in 13 cases and extensive bone destruction was found in 3 cases. Compared with adjacent muscles, T 1WI of all 16 cases showed isointense, with focal hypointense in 3 cases. On T 2WI, the tumor was graded as isointense in 9 cases, hyperintense in 7 cases, with lower inner septal in 6 cases. Enhancement was graded as mild in 11 cases, moderate in 5 cases.MRI Enhancement images showed mild enhancement in 11 cases, moderate enhancement in 5 cases, heterogeneous enhancement in 6 cases, and homogeneous enhancement in 10 cases. For DCE-MRI of 14 cases, there were 10 cases of Ⅲ type and 4 cases of Ⅱ type of the TIC. The ADC value of 14 cases was (1.02±0.27)×10 -3 mm 2/s. The Ki-67 index was 48%±21%. No correlation was observed between Ki-67 index and ADC value ( r=-0.38, P=0.183). Conclusions:SMARCB1-deficient carcinomas are mostly centered in the nasal and ethmoid region of anatomic distribution. Tendency to be infiltrative the adjacent bone structure with invasive bone reaction, mild to moderate heterogeneous enhancement, T 2WI with lower inner septal, and Ⅲ types of TIC are certain suggestive imaging features of the entity.

Objective:To assess the clinical and imaging features of NUT gene-related sinonasal carcinomas (NUT midline carcinome).Methods:The clinical data and pretreatment imaging findings of 5 cases with pathologically proven NUT sinonasal carcinomas were analyzed retrospectively in Beijing Tongren Hospital, Capital Medical University from January 2016 to December 2020. Of 5 cases, the tumors affected 4 females and 1 male with an age range of 15 to 48 years (median 19 years). Clinical data of all cases were available before surgery with both CT and MR examination. Tumor location, CT density, boney change, calcification, tumor size, T 1WI, T 2WI and diffusion weighted imaging (DWI) signal intensity, appearance diffusion coefficient (ADC), type of time intensity curve (TIC) of dynamic contrast-enhanced (DCE)-MRI were evaluated. Results:All five cases belonged to T4 stage of the clinic TNM system. The locations were nasal cavity ethmoid, sphenoid and maxillary sinus ( n=1), nasal and maxillary sinus ( n=1), nasal cavity and ethmoid sinus ( n=3). Iso-attenuated in 3 cases, heterogeneous with local necrosis in 2 cases, and heterogeneous with calcification in 3 cases on CT imaging. Bone erosion was found in 4 cases, and bone erosion with destruction in 1 case. The tumor sizes ranged from 4.2 to 4.9 cm (median 4.5 cm) on MR axial imaging. On T 1WI, 5 cases showed isointense compared with adjacent temporal muscles, with focal hypointense in 2 cases. On T 2WI, the tumor was graded as isointense in 3 cases, and hyperintense in 2 cases. Heterogeneous enhancement in all cases with mild in 3 cases, and moderate in 2 cases on postcontrast MR imaging. On DCE-MRI of 5 cases, there were 3 cases of type Ⅲ (washout-shaped curves), and 2 cases of type Ⅱ of the TIC (plateau-shaped curves). The range of ADC values was from 0.63×10 -3 to 1.17×10 -3 mm 2/s, and median ADC value was 0.84×10 -3 mm 2/s, of 5 cases with varying degrees of high signal on DWI. The Ki-67 index ranged from 30% to 80% of the tumor. An immunohistochemical study showed that the tumor cells of 5 cases were all positive for both NUT and INI-1 genes. One case was performed with biopsy and followed by chemotherapy, four cases were performed with surgery, combined with the following chemotherapy, and one also was implemented with radiation therapy. The follow-up time was 7-16 months. Five cases were all alive during the follow-up. Conclusions:The NUT midline sinonasal tract carcinoma is a rare, gene-related solid malignant tumor. The tumor is more commonly seen in young patients, mostly centered in the nasal and ethmoid region with invasive growth, more calcification on CT, and heterogeneous enhancement on MRI. These findings are some characteristics of the tumor.

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.