[Gene-age interaction study of breast cancer prognosis based on epigenomic data].

Objective: Exploring gene-age interactions associated with breast cancer prognosis based on epigenomic data. Methods: Differential expression analysis of DNA methylation was conducted using multiple independent epigenomic datasets of breast cancer from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The false discovery rate (FDR) method was used for multiple corrections, retaining differentially methylated sites with q-FDR≤0.05. A three-stage analytic strategy was implemented, using a multivariable Cox proportional hazards regression model to examine gene-age interactions. In the discovery phase, signals with q-FDR ≤ 0.05 were screened out using TCGA-BRCA database. In validation phaseⅠ, the interaction was validated using GSE72245 data, with criteria of P≤0.05 and consistent effect direction. In validation phaseⅡ, the signals were further validated using GSE37754 and GSE75067 data. A prognostic prediction model was constructed by incorporating clinical indicators and interaction signals. Results: The three-stage analytic strategy identified a methylation site (cg16126280EBF1), which interacted with age to jointly affect the overall survival time of patients (interaction HR= 1.001 1,95%CI:1.000 7-1.001 5,P<0.001). Stratified analysis by age showed that the effect of hypermethylation of cg16126280EBF1 was completely opposite in younger patients (HR=0.550 5, 95%CI: 0.383 8-0.789 6, P=0.001) and older patients (HR=2.166 5, 95%CI: 1.285 2-3.652 2, P=0.004). Conclusions: The DNA methylation site cg16126280EBF1 exhibits an interaction with age, jointly influencing the prognosis of breast cancer in a complex association pattern. This finding contributes new population-based evidence for the development of age-specific targeted drugs.

[Advances in the application of minimal residual disease in non-metastatic colorectal cancer].

In recent years, the application of minimal residual disease (MRD) in solid tumors has gained widespread attention. MRD typically refers to the presence of residual cancer cells that remain undetectable by imaging after curative treatments, such as surgical resection. The presence of MRD post-surgery is significantly associated with an increased risk of tumor recurrence. In colorectal cancer, circulating tumor DNA (ctDNA) serves as an effective marker for assessing MRD, particularly in non-metastatic (stages I-III) colorectal cancer. As a real-time, accurate, and convenient biomarker, ctDNA can effectively predict tumor recurrence, guide postoperative adjuvant chemotherapy decisions, and provide crucial information for recurrence monitoring. The application prospects of ctDNA detection technology are vast, promising more precise and individualized treatment plans for colorectal cancer patients. This article comprehensively analyzes the progress in the application of ctDNA for detecting MRD in non-metastatic colorectal cancer patients, elaborates on its guiding role in clinical treatment decisions, and envisions the future development directions in this field.

[Analysis of therapeutic effects of allogeneic hematopoietic stem cell transplantation in 12 patients with DEK-NUP214 fusion gene positive acute myeloid leukemia].

Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10(8)/kg, and the number of CD34(+) cells was 3.29 (2.53-6.10) ×10(6)/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.

[Analysis of the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome with blastomycosis and survival comparison of different subtypes after the WHO 2022 reclassification].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022. Methods: A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed. Results: ① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype (P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points (P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ (P<0.001, HR=5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% -80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively (P=0.690) . Conclusion: Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient's OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.

[Inhibitory effect of 5-hydroxy-6,7-dimethoxyflavone on H1N1 influenza virus-induced ferroptosis and inflammation in A549 cells and its possible mechanisms].

OBJECTIVE: To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone (5-HDF), a compound extracted from Elsholtzia blanda Benth., against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action. METHODS: 5-HDF was extracted from Elsholtzia blanda Benth. using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses. In an A549 cell model of H1N1 influenza virus infection (MOI=0.1), the cytotoxicity of 5-HDF was assessed using MTT assay, and its effect on TRAIL and IL-8 expressions was examined using flow cytometry; Western blotting was used to detect the expression levels of inflammatory, apoptosis, and ferroptosis-related proteins. In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 µL H1N1 virus at the median lethal dose, the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight, lung index, gross lung anatomy and lung histopathology were observed. RESULTS: 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 µg/mL. In H1N1-infected A549 cells, treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65, lowered the expressions of IL-8, enhanced the expression of anti-ferroptosis proteins (SLC7A11 and GPX4), and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL. In H1N1-infected mice, treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies. CONCLUSION: 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis, inflammatory responses, and apoptosis via upregulating SLC7A11 and GPX4, inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK, and decreasing the expression of cleaved caspase3 and cleaved PARP.

[Efficacy of venetoclax-based induction regimen in newly diagnosed pediatric acute myeloid leukemia].

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [M (Q1, Q3)] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P>0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P=0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference (P=0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission (OR=0.126, 95%CI: 0.025-0.629). FLT3 mutation was not conducive to morphological remission (OR=5.832, 95%CI: 1.778-19.124) and negative MRD (OR=4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.

[Coenzyme Q10 alleviates depression-like behaviors in mice with chronic restraint stress by down-regulating the pyroptosis signaling pathway].

OBJECTIVE: To explore the neuroprotective effect of coenzyme Q10 and its possible mechanism in mice with chronic restraint stress (CRS). METHODS: Mouse models of CRS were treated with intraperitoneal injections of coenzyme Q10 at low, moderate and high doses (50, 100 and 200 mg/kg, respectively, n=8), VX765 (a caspase-1 specific inhibitor, 50 mg/kg, n=8), or fluoxetine (10 mg/kg, n=8) on a daily basis for 4 weeks, and the changes in depression-like behaviors of the mice were assessed by sugar water preference test, forced swimming test and tail suspension test. The expression of glial fibrillary acidic protein (GFAP) in the hippocampus of the mice was detected using immunohistochemistry, and the number of synaptic spines was determined with Golgi staining. Western blotting was performed to detect the changes in the expressions of GFAP and pyroptosis-related proteins in the hippocampus, and the colocalization of neurons and caspase-1 p10 was examined with immunofluorescence assay. RESULTS: Compared with the normal control mice, the mouse models of CRS showed significantly reduced sugar water preference and increased immobility time in forced swimming and tail suspension tests (P < 0.05), and these depression-like behaviors were obviously improved by treatment with coenzyme Q10, VX765 or FLX. The mouse models showed a significantly decreased positive rate of GFAP and lowered GFAP protein expression in the hippocampus with obviously decreased synaptic spines, enhanced expressions of GSDMD-N, caspase-1 and IL-1ß, and increased colocalization of neurons and caspase-1 p10 (all P < 0.05). All these changes were significantly ameliorated in the mouse models after treatment with Q10. CONCLUSION: Coenzyme Q10 can alleviate depression-like behaviors in mice with CRS by down-regulating the pyroptosis signaling pathway.

[The prognostic evaluation of coronary artery calcification score and CT fractional flow reserve for patients with stable coronary artery disease].

Objective: To investigate the prognostic value of coronary artery calcium score (CACS) and computed tomography-derived fractional flow reserve (CT-FFR) for major adverse cardiovascular events (MACE) in patients with stable coronary artery disease (CAD). Methods: The data for this prospective study were derived from a prospective clinical trial at a single center. This trial enrolled stable CAD patients who underwent coronary CT angiography (CCTA) in General Hospital of Eastern Theater Command from April 2018 to March 2019 and had coronary artery stenosis of 25%-80%. Patients were assigned to either the control group or trial group according to CCTA time. Patients in control group were provided with only a standard CCTA report, while patients in trial group were provided with both a standard CCTA report and the corresponding CT-FFR results. The study included patients who underwent ECG-gated calcium scoring CT scans in this trial. CT-FFR value at 2 cm distal to the narrowest stenosis of each vessel was calculated. The minimum CT-FFR value was recorded as the patient level and CT-FFR≤0.80 was defined as a positive result. All patients were followed up for MACE, including all-cause death, nonfatal myocardial infarction, and acute coronary syndrome leading to unplanned revascularization. Multivariable Cox proportional hazards regression analysis was used to identify variables associated with MACE occurrence, and the Concordance index (C-index) was used to represent the performance of the models for predicting MACE occurrence based on clinical, anatomical, and CT-FFR parameters. Results: A total of 783 patients were finally statistically analyzed, with a age of (62.0±10.8) years, of whom 64.6% (506 cases) were male. There were 383 patients in the trial group and 400 patients in the control group, with a median follow-up time of 35.3 months. A total of 81 MACE cases occurred during the follow-up. The incidence of MACE in trial group (8.1%, 31/383) was significantly lower than that in control group (12.5%, 50/400)(χ2=4.095, P=0.043). CACS≥300, stenosis≥70% and CT-FFR≤0.80 [HR (95%CI) were 2.14 (1.01-4.52), 5.38 (3.44-8.42) and 16.91 (9.21-31.04), all P<0.05] showed predictive value for MACE. The predictive ability of the CT-FFR model is significantly better than that of the CACS model and the stenosis degree model [C-index (95%CI) were 0.850 (0.823-0.874), 0.653 (0.618-0.686) and 0.718 (0.685-0.749), all P≤0.001]. The comprehensive model with added CACS and stenosis degree did not significantly improve the predictive value of the CT-FFR model [C-index (95%CI) were 0.867 (0.841-0.890), 0.850 (0.823-0.874), P=0.584]. Conclusions: CT-FFR has a high predictive value for MACE in patients with stable CAD, the combination of CT-FFR and CACS did not increase the predictive power of CT-FFR.

[Epidemiological characteristic of viral encephalitis in children and adolescents in Henan Province, 2012-2023].

Objective: To understand the epidemiological characteristics and spatiotemporal distribution of viral encephalitis in children and adolescents in Henan Province from 2012 to 2023. Methods: The information about viral encephalitis cases from October 1, 2012 to July 26, 2023 were collected from Zhengzhou Children's Hospital (National Children's Regional Medical Center),Henan Provincial Children's Hospital for the analyses on temporal distribution the cases, the severe illness rate, age distribution, pathogen type and imaging findings of the cases. Results: A total of 6 276 cases of viral encephalitis were included in this study after excluding cases with incomplete information. The cases mainly originated from Zhengzhou (38.96%), followed by Zhoukou (9.93%), Xuchang (8.68%), Zhumadian (7.90%) and Pingdingshan (7.39%). The cases in boys accounted for 62.13% and the cases in girls accounted for 37.87%. Most cases (72.45%) occurred in age group 7-13 years. The overall rate of severe illness cases was 4.51% from 2012 to 2023. There were significant differences in severe illness cases among different areas and years (χ2=5.33,P=0.021; χ2=48.14,P<0.001). Enteroviruses were mainly detected (31.57%), in which Coxsackie virus was predominant (58.37%). Imaging findings showed that cerebral hemisphere damage was most common in children and adolescents with viral encephalitis (54.93%). Conclusions: From 2012 to 2023, more cases of viral encephalitis occurred in boys in Henan. Children and adolescents aged 7-13 years were the main affected group. The prevention of enteroviruses infection, especially Coxsackie virus, needs to be strengthened. Special attention should be paid to the prevention of cerebral hemisphere damage after viral encephalitis diagnosis.

Retraction Note: LncRNA UCA1 affects osteoblast proliferation and differentiation by regulating BMP-2 expression.

The article "LncRNA UCA1 affects osteoblast proliferation and differentiation by regulating BMP-2 expression", by R.-F. Zhang, J.-W. Liu, S.-P. Yu, D. Sun, X.-H. Wang, J.-S. Fu, Z. Xie, published in Eur Rev Med Pharmacol Sci 2019; 23 (16): 6774-6782-DOI: 10.26355/eurrev_201908_18715-PMID: 31486475 has been retracted by the authors for the following reasons: - The data presented in the manuscript require further validation, which may affect the results. After careful consideration, we have decided to withdraw it to ensure its reliability and reproducibility. All authors concur with this decision. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18715.

[Incidence of common gene mutations in early-onset colorectal cancer and the association with cancer survival: a meta-analysis].

Objective: The incidence of early-onset colorectal cancer (EOCRC) is increasing globally; however, the molecular characteristics and prognosis of sporadic EOCRC are unclear. In this systematic review and meta-analysis, we aimed to investigate the incidence of gene mutations and their association with cancer survival in sporadic EOCRC, focusing on six common gene mutations (TP53, BRAF, KRAS, NRAS, PTEN, and APC). Methods: Ovid Embase and Ovid Medline electronic databases were searched for studies involving patients with sporadic EOCRC (i.e., diagnosed with colorectal cancer before the age of 50 years and with no evidence of hereditary syndromes predisposing to colorectal cancer). The included articles were evaluated using quality assessment tools. Meta-analysis was performed using random-effects and fixed-effects models. Cochran's Q statistic and the I2 index were used to assess heterogeneity. The incidence of the six common gene mutations listed above in sporadic EOCRC and their association with cancer survival were evaluated. Results: (1) Incidence of specific gene mutations in sporadic EOCRC. A total of 34 articles were included in this meta-analysis. The incidence of APC gene mutation was 36% (from 13 articles, 95%CI: 19%-55%, P=0.043); of KRAS gene mutation 30% (from 26 articles, 95%CI: 24%-35%, P=0.190); of BRAF gene mutation 7% (from 18 articles, 95%CI: 5%-11%, P=0.422); of NRAS gene mutation 4% (from five articles, 95%CI: 3%-5%, P=0.586); of PTEN gene mutation 6% (from six articles, 95%CI: 4%-10%, P=0.968); and of TP53 gene mutation 59% (from 13 articles, 95%CI: 49%-68%, P=0.164). (2) Association between gene mutations and survival in sporadic EOCRC. A total of six articles were included in this meta-analysis. Compared with wild-type BRAF, mutant BRAF was significantly associated with increased overall mortality risk in patients with EOCRC (pooled HR=2.85, 95%CI: 1.45-5.60, P=0.002). Subgroup analysis showed that the incidence of BRAF gene mutation was higher in Eastern than in Western countries, whereas the incidence of TP53, KRAS, NRAS, and APC gene mutations was lower. There was no significant difference in the incidence of PTEN gene mutation between different regions. Conclusion: Compared with colorectal cancer occurring in the general population, the incidence of APC and KRAS mutations is lower in EOCRC, whereas the incidence of TP53 mutation remains consistent. BRAF mutation is associated with increased overall mortality risk in patients with EOCRC.

Biocontrol of strawberry Botrytis gray mold and prolong the fruit shelf-life by fumigant Trichoderma spp.

Objectives To screen high active volatile organic compounds (VOCs)-producing Trichoderma isolates against strawberry gray mold caused by Botrytis cinerea, and to explore their antagonistic mode of action against the pathogen. VOCs produced by nine Trichoderma isolates (Trichoderma atroviride T1 and T3; Trichoderma harzianum T2, T4 and T5; T6, T7, T8 and T9 identified as Trichoderma asperellum in this work) significantly inhibited the mycelial growth (13.9-63.0% reduction) and conidial germination (17.6-96.3% reduction) of B. cinerea, the highest inhibition percentage belonged to VOCs of T7; in a closed space, VOCs of T7 shared 76.9% and 100% biocontrol efficacy against gray mold on strawberry fruits and detached leaves, respectively, prolonged the fruit shelf-life by 3 days in presence of B. cinerea, completely protected the leaves from B. cinerea infecting; volatile metabolites of T7 damaged the cell membrane permeability and integrity of B. cinerea, thereby inhibiting the mycelial growth and conidial germination. Gas chromatography-mass spectrometry (GC-MS) analysis revealed the VOCs contain 23 potential compounds, and the majority of these compounds were categorised as alkenes, alcohols, and esters, including PEA and 6PP, which have been reported as substances produced by Trichoderma spp. T. asperellum T7 showed high biofumigant activity against mycelial growth especially conidial germination of B. cinerea and thus protected strawberry fruits and leaves from gray mold, which acted by damaging the pathogen's plasma membrane and resulting in cytoplasm leakage, was a potential biofumigant for controlling pre- and post-harvest strawberry gray mold.

Genetic analysis of a Kaijiang duck conservation population through genome-wide scan.

1. The Kaijiang duck is a native Chinese breed known for its excellent egg laying performance, killing-out percentage (88.57%), and disease resistance. The assessment of population genetic structure is the basis for understanding the genetics of indigenous breeds and for their protection and management.2. In this study, whole-genome sequencing was performed on 60 Kaijiang ducks to identify genetic variations and investigate the population structure. Homozygosity (ROH) analysis was conducted to assess inbreeding levels in the population.3. The study revealed a moderate level of inbreeding, indicated by an average inbreeding coefficient of 0.1043. This may impact the overall genetic diversity.4. Genomic Regions of Interest identified included 168 genomic regions exhibiting high levels of autozygosity. These regions were associated with processes including muscle growth, pigmentation, neuromodulation, and growth and reproduction.5. The significance of these pathways indicated their potential role in shaping the desirable traits of the Kaijiang duck. These findings provide insights into the genetic basis of the Kaijiang duck's desirable traits and can inform future breeding and conservation efforts.

Antioxidant effect of dimethyl fumarate in pentylenetetrazole-kindled epilepsy mice and is activated by nuclear factor erythroid 2-related factor 2 pathway.

This study was designed to examine the anti-oxidative stress effect of dimethyl fumarate (DMF) on pentylenetetrazole (PTZ)-induced epileptic mice, and to evaluate the correlation of its mechanism with the nuclear factor E2-related factor 2 (Nrf2)-mediated signaling pathway. The experimental mice were separated into three groups: control, model, and DMF groups. Mice in the model group were administered PTZ to establish an epilepsy model, mice in the DMF group were administered DMF concurrently when modeling, and mice in the control group were administered a 0.9% NaCl solution. The latency, severity, and frequency of epileptic seizures in mice after each treatment were recorded, and the modelling success rate was computed at the conclusion of the experiment. The mice were euthanized, their levels of malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), 8-hydroxy-deoxyguanosine (8-OHdG), and Nrf2 were measured, and the electron microscope was used to examine the mitochondrial damage of brain tissue. The latency of epileptic seizures was longer in the DMF group compared to the model group (P<0.05). The levels of MDA and ROS in the DMF group were lower than those in the model group (P<0.0001), and the activity of SOD in the DMF group was higher than that in the model group (P<0.0001); however, the levels of MDA and ROS were elevated and the activity of SOD was lower in both groups relative to the control group. The levels of 8-OHdG were lower in the DMF group than the model group (P<0.0001), however, the levels were higher in both groups compared to the control group. Mitochondrial abnormalities were more prevalent in the model group than in the DMF group, and more prevalent in both groups compared to the control group. The DMF group contained more Nrf2 content than the model group (P<0.0001), and both groups contained more Nrf2 than the control group. We concluded that the mechanism by which DMF reduced the level of oxidative stress in epileptic mice might involve the Nrf2-mediated signaling pathway.

[Dynamic observation on capillarization of liver sinusoidal endothelial cells induced by Echinococcus multilocularis infection].

OBJECTIVE: To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. METHODS: Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson's trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. RESULTS: Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson's trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/µm2 and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/µm2 and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). CONCLUSIONS: E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

[L-DEP regimen salvage therapy for refractory primary hemophagocytic lymphohistiocytosis triggered by Epstein-Barr virus infection in 4 children].

Objective: To analyze the efficacy and safety of the L-DEP regimen (asparaginase, liposome doxorubicin, etoposide and methylprednisolone) as a salvage therapy for the refractory primary hemophagocytic lymphohistocytosis triggered by Epstein-Barr virus infection (EBV-pHLH) in children. Methods: In this retrospective case study, clinical and laboratory data before and after L-DEP regimen of 4 children diagnosed with EBV-pHLH in Beijing Children's hospital between January 2016 and June 2022 were collected, and the efficacy and safety of L-DEP regimen for the treatment of EBV-pHLH were analyzed. Results: Among 4 patients, there were 3 females and 1 male with the age ranged from 0.8 to 7.0 years. Two of them showed compound heterozygous mutations of PRF1, one with a heterozygous mutation of UNC13D, one homozygous mutation of ITK. Before the L-DEP therapy, all of them had anemia and a soaring level of soluble CD25, 3 patients had neutropenia and thrombopenia, 3 patients had a high level of ferritin, 3 patients had hypofibrinogenemia and 1 patient had hypertriglyceridemia. After receiving 1 or 2 cycles of L-DEP treatment, three achieved remission, including complete remission (1 case) and partial remission (2 cases), and the other one had no remission. The levels of blood cell counts, soluble CD25, triglyceride, fibrinogen and albumin were recovered gradually in 3 patients who got remission. All four patients underwent hematopoietic stem cell transplantation (HSCT) after L-DEP regimen, and three survived. All patients had no severe chemotherapy related complications. The main side effects were bone marrow suppression, infection and pancreatitis, which recovered after appropriate treatments, apart from one who died from severe infection after urgent HSCT. Conclusion: L-DEP regimen could be served as an effective and safe salvage treatment for refractory pediatric EBV-pHLH, and also provide an opportunity for patients to receive HSCT.

Study on the construction of nomogram prediction model for prognostic assessment of heart failure patients based on serological markers and echocardiography.

OBJECTIVE: We aimed to construct a nomogram prediction model for prognostic assessment of patients with heart failure (HF) based on serological markers and echocardiography. PATIENTS AND METHODS: A total of 200 HF patients admitted to the Second Affiliated Hospital of Nanchang University from January 2018 to January 2020 were selected as the research objects. According to the New York Heart Association (NYHA) cardiac function classification, they were divided into 3 groups, including 65 cases of grade II, 97 cases of grade III, and 38 cases of grade IV. Three groups of echocardiographic parameters were compared [including left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic volume (LVESV)], differences in serum markers brain natriuretic peptide (BNP), soluble growth-stimulating expression gene 2 (sST2) and the Modified Early Warning Score (MEWS). The patients were divided into two groups according to their clinical outcomes during the follow-up period, including 52 cases in the death group and 148 cases in the survival group. The clinical data of the two groups were compared, and multi-factor logistic regression analysis was performed to screen out the independent risk factors affecting the patient's death. A nomogram model of the patient's mortality risk was constructed based on the independent risk factors. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the discrimination and accuracy of the nomogram model. RESULTS: As the cardiac function class of elderly chronic heart failure (CHF) patients increases, LVEDD, LVESD, sST2, and MEWS increase and LVEF decreases (p<0.05). Multifactor analysis results showed that LVEF, LVEDD, sST2, and MEWS were independent factors affecting the clinical outcome of patients. The AUCs predicted using LVEF, LVEDD, sST2, and MEWS alone were 0.738, 0.775, 0.717, 0.831, and 0.768, respectively. There is a certain degree of discrimination, and the model has extremely high accuracy. CONCLUSIONS: MEWS, LVEDD, and sST2 increase as the NYHA cardiac function grade of HF patients increases and LVEF decreases, which can reflect the severity of the disease to a certain extent. Additionally, the nomogram model established based on this has a high predictive value for the long-term prognosis of patients and can formulate effective intervention measures for quantitative values.

A high resolution reaction microscope with universal two-region time-focusing method.

This paper presents a novel reaction microscope designed for ion-atom collision investigations, established at the Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China. Its time-of-flight (TOF) spectrometer employs an innovative flight-time focusing method consisting of two acceleration regions, providing optimal time focusing conditions for charged fragments with diverse initial velocities. The TOF spectrometer's axis intentionally tilts by 12° relative to the ion beam direction, preventing potential obstructions from the TOF grid electrodes. The introduced focusing method allows for a flexible time-focusing TOF spectrometer design without restricting the length ratio of the two regions. In addition, this configuration in our case significantly suppresses noise on the recoil ion detector produced by residual gas in the ion beam trajectory, which is a considerable challenge in longitudinal spectrometers. In a test experiment on the single electron capture reaction involving 62.5 keV/u He2+ ions and a helium atomic beam, the recoil longitudinal momentum resolution achieved 0.068 atomic units. This novel configuration and successful test run show excellent precision for ion-atom collision studies.