ObjectiveTo clarify the expression of TRIM28 in non-M3 acute myeloid leukemia （AML） and its correlation with clinical indicators and prognosis， and to further explore the effect of TRIM28 expression levels on the proliferation and apoptosis of AML cells using small interfering RNA. MethodsThe GSE34577 dataset was analyzed using R software to compare TRIM28 expression between healthy controls and non-M3 acute myeloid leukemia （AML） patients. Clinical samples from non-M3 AML patients were collected， with TRIM28 expression levels measured using real-time quantitative PCR （qPCR）. The analysis focused on correlations between TRIM28 expression and various clinical indicators， treatment efficacy， and patient prognosis. Furthermore， small interfering RNA （siRNA） technology was employed to downregulate TRIM28 expression in human primary AML cells （HL60 cell line）. The effects on cell proliferation and apoptosis were then assessed through CCK-8 assays and flow cytometry， respectively. ResultsThe results showed that TRIM28 was up-regulated in non-M3 AML of both online database GSE34577 and clinical samples （P<0.000 1）， TRIM28 expression of new diagnosis group and relapsed refractory group was higher than iron deficiency anemia group （P<0.01）， and there was no significance between different French-American-British classification systems subtype. TRIM28 expression was higher in non-M3 AML patients with a poor genetic prognosis stratified as moderate than in the good prognosis group， and TRIM28 expression was associated with NPM1 combined with the FLT3-ITD mutation， positively correlated with age， bone marrow blast， peripheral blood blast and white blood cell， negatively correlated with hemoglobin. In addition， interference TRIM28 greatly inhibited cell proliferation and promoted cell apoptosis. ConclusionThis study reveals that TRIM28 is highly expressed in non-M3 AML and associated with prognosis， and plays a key role in the proliferation and apoptosis of AML cells， suggesting that TRIM28 may serve as a novel therapeutic target for non-M3 AML.

Objective To explore the clinical values of non-invasive myocardial work (MW) and tissue motion annular displacement (TMAD) in evaluation of anthracycline therapy-related cardiac dysfunction in patients with non-Hodgkin lymphoma. Methods A total of 62 patients with non-Hodgkin lymphoma who received standardized chemotherapy based on doxorubicin. Two and three dimensional transthoracic echocardiography, along with two dimensional speckle tracking echocardiography, were performed one day before chemotherapy and at 3, 6, and 9 months after chemotherapy to assess left ventricular ejection fraction, global longitudinal strain (GLS), MW parameters, and TMAD. Logistic regression analysis was used to evaluate the risk factors for cancer therapy-related cardiac dysfunction (CTRCD). The receiver operating characteristic curve was used to assess the diagnostic values of MW- and TMAD-related parameters for CTRCD. Results Compared to baseline, GLS, global work index (GWI), global constructive work (GCW), global work efficiency (GWE), TMAD at midpoint (TMADmid), and TMADmid percentage of left ventricular long-axis diameter (TMADmid%) decreased at 3 months after chemotherapy, while global wasted work (GWW) increased at 6 months after chemotherapy (P＜0.05). Logistic regression analysis showed that the relative reduction in GLS and TMADmid% at 3 months after chemotherapy were independent predictors for CTRCD （P＜0.05), while MW parameters were not independent predictors for CTRCD. GLS reduction≥10.3% and TMADmid% reduction≥15.8% at 3 months after chemotherapy predicted CTRCD with 0.866 and 0.824 of area under the curve (AUC), 92% and 75% of sensitivity, and 74% and 80% of specificity, respectively. AUC of combination of two indexes improved to 0.905, with 75% of sensitivity and 90% of specificity. Conclusions In non-Hodgkin lymphoma patients, the combination of GLS and TMADmid% is helpful of predicting CTRCD early, TMAD may be a novel diagnostic index for CTRCD, and GLS has superior predictive performance than MW for CTRCD.

Objective: To investigate the effects of different doses of X ⁃rays irradiation combined with allogeneic lymphocyte infusion on the establishment of aplastic anemia in mice. Methods: Forty BALB/c mice were randomly divided into four groups : the 3 Gy group (n = 9) , the 4 Gy group (n = 9) , the 5 Gy group (n = 10) , and the con⁃trol group (n = 12) . In the 3 Gy , 4 Gy , and 5 Gy groups , the experimental mice were exposed to corresponding do⁃ses of X ⁃ray and then intravenously infused with 0. 2 mL mixed suspension of the thymus and spleen cells from DBA/2 mice , at a concentration of 1 × 107 cells/mL , within 4 hours after irradiation. The control group did not un⁃dergo X ⁃ray irradiation and infused with an equivalent volume of physiological saline instead. Blood samples were collected from the orbital venous plexus of BALB/c mice and analyzed using an animal automated hematology analy⁃zer to measure peripheral blood parameters , including red blood cells ( RBC) , white blood cells ( WBC) , and platelets (PLT) . The general condition of mice was monitored daily , and survival rates were recorded for each group. At the experimental endpoint , the tibias were harvested for hematoxylin and eosin (HE) staining , while the femurs were used to prepare bone marrow smears for morphological examination. For the 5 Gy group , T ⁃cell subsets(ELISA) at the endpoint. Results : In the 3 Gy group , pancytopenia was observed , but platelet recovery occured rapidly , returning to normal levels by day 17 post⁃modeling. No deaths occurred during the observation period. At myeloid⁃to⁃erythroid (M/E) ratio , and no significant morphological abnormalities were noted in cells at any devel⁃with hematopoietic cells. In the 4 Gy group , pancytopenia persisted throughout the observation period. The survival rate was 90% . Endpoint analysis showed hypocellular marrow by morphological examination. HE staining indicated minimal fatty infiltration in the bone marrow tissue. In the 5 Gy group , pancytopenia was observed , though erythro⁃cyte counts returned to normal levels by day 24. The survival rate during the observation period was 50% . Endoint analysis revealed vacuolization of marrow particles and reduced hematopoietic cells with predominantly non⁃hematopoietic cells in bone marrow morphology. HE staining demonstrated severe fatty infiltration in the bone mar⁃row tissue , with scarcity of immature cells and hematopoietic precursor cells. Flow cytometry analysis showed a de⁃creased proportion of CD4 + T cells (% ) and an increased proportion of CD8 + T cells (% ) . ELISA confirmed elevated secretion of negative hematopoietic regulators : interferon⁃gamma ( IFN⁃γ) and tumor necrosis factor⁃alpha (TNF⁃α ) . Conclusion Combined administration of varying radiation doses with allogeneic lymphocyte infusion consistently induced peripheral blood cytopenia in mice , characterized by reductions in RBC , WBC , and PLT counts. Integrated analysis of bone marrow morphology , histopathological assessment via HE staining , and immuno logical parameters confirmed that a mouse model of aplastic anemia can be successfully established using 5 Gy X ⁃ ray irradiation coupled with infusion of 2 × 106 allogeneic lymphocytes.

Objective:To explore the therapeutic effect of compound Kuijie Ankang Decoction on ulcerative colitis (UC) model mice by non targeted metabonomics; To explore its mechanism.Compound Kuijie Ankang.Methods:The mice were randomly divided into blank control group, model group, Kuijie Ankang Decoction group and sulfasalazine group, with 12 mice in each group. Except the blank control group, the other groups were given 1.5% DSS solution for free drinking to prepare UC model. After successful modeling, Kuijie Ankang Decoction group was intragastrically administered with compound Kuijie Ankang Decoction of 9.68 g/kg, sulfasalazine group was intragastrically administered with sulfasalazine capsule suspension of 320 mg/kg, model group and blank control group were intragastrically administered with equal volume of purified water, once a day, for 7 consecutive days. The body mass and disease activity index (DAI) score of mice were measured. ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the colon tissue of mice; the protein expressions of Claudin-1 and Zo-1 in colon tissue were detected by immunofluorescence method. HE staining was used to observe the pathological changes in the colon, and UHPLC-OE-MS technology was used to analyze the endogenous metabolite structure of mouse colon tissue, differential metabolites and related metabolic pathways were screened.Results:Compared with the model group, the colon length in Kuijie Ankang Decoction group and sulfasalazine group increased ( P<0.01), the DAI score decreased ( P<0.01), the levels of TNF-α, IL-1β and IL-6 in colon tissue decreased ( P<0.01), the level of IL-10 increased ( P<0.01), and the average optical density of Claudin-1 and Zo-1 protein increased ( P<0.01 or P<0.05). Metabolomics analysis identified 26 potential differential metabolites, including nicotinamide adenine dinucleotide, guanine, gamma aminobutyric acid, and thiamine, affecting 26 key metabolic pathways, including lysine biosynthesis, thiamine metabolism, cysteine and methionine metabolism. Conclusion:Kuaijie Ankang Decoction may improve metabolites such as Gamma aminobutyric acid and thiamine through metabolic pathways such as lysine biosynthesis to alleviate inflammatory reactions, thereby exerting therapeutic effects on ulcerative colitis in mice.

Hepatic ischemia-reperfusion injury(IRI)is a pathological phenomenon that commonly occurs during liver surgery and transplantation.It leads to serious tissue damage and affects liver function.The mechanisms behind IRI are complex,involving oxida-tive stress,inflammatory responses,and calcium homeostasis disorder.Recently,scientists have paid more attention to the role of endo-plasmic reticulum stress(ERS)in IRI.ERS activates three classical signaling pathways,PERK,IRE1,and ATF6,through the unfolded protein response(UPR),aiming to preliminarily restore endoplasmic reticulum homeostasis and protect cells.However,if the stress re-sponse is excessive or persistent,ERS can activate apoptosis signaling pathways,such as CHOP and Bax/Bak,worsening cell injury.Additionally,ERS is closely related to other cellular stress responses,such as autophagy and oxidative stress,which jointly affect the survival and death of hepatocytes.Regulation of ERS,especially interventions targeting the three UPR pathways,is considered as a po-tential therapeutic pathway for alleviating hepatic IRI.Pharmacological interventions,such as 4-phenylbutyric acid and taurocholic acid,and gene therapies,such as knocking out PERK or IRE1,have shown positive effects in protecting liver function while inhibiting ERS.This paper reviews the mechanism of action of ERS in hepatic IRI,focuses on the specific roles of the three UPR pathways and their potential as therapeutic targets,and explores the future of re-lated therapeutic strategies.

Objective To identify the key biomarkers for diagnosing chronic obstructive pulmonary disease(COPD)complicated with pulmonary arterial hypertension(PAH)using bioinformatics,and validate their clinical significance.Methods High-throughput sequencing data analysis was employed to identify differentially expressed genes(DEGs)in COPD-PAH.Functional enrichment analysis was then conducted to explore the biological functions of these DEGs.Machine learning methods,including least absolute shrinkage and selection operator(LASSO),random forest(RF),and support vector machine-recursive feature elimination(SVM-RFE),were utilized to screen 5 potential biomarkers.Single-cell analysis was performed to reveal the expression patterns of these key genes in macrophages.The clinical significance of these biomarkers was further validated using peripheral blood mononuclear cells(PBMC)data.A mouse model of COPD-PAH was established using hypoxia exposure.Sixteen mice(either sexes,8 weeks old,weighing 20～22 g)were randomly divided into a hypoxia group[O2(10.0±0.5)%,COPD-PAH,n=8]and a normoxia group(COPD,n=8).Immunofluorescence assay was used to label the key biomarkers,and their expression levels were quantified.Results A total of 28 DEGs(|Log2FC|≥2,P<0.05)were identified in COPD-PAH patients.Functional enrichment analysis indicated that DEGs in COPD were primarily associated with major histocompatibility complex(MHC)Ⅱ and cell division,and involved in lysosomes,oxidative phosphorylation,and cell cycle pathways(P<0.05).Machine learning identified 5 potential biomarkers(GRN,KLF4,SHTN1,LRP1,and GPNMB),and subsequent single-cell analysis revealed that these markers exhibited reverse expression patterns during disease progression.A nomogram model constructed based on PBMC data yielded an area under the curve(AUC)of 0.907 in diagnosing COPD-PAH.GRN,KLF4,SHTN1,LRP1 and GPNMB were significantly upregulated in the COPD-PAH group(P<0.05).Conclusion GRN,KLF4,SHTN1,LRP1 and GPNMB are identified as key biomarkers for the prediction and diagnosis of COPD-PAH,which providing new insights for the clinical and treatment of the condition.

The development of forensic medicine is crucial to the national welfare,people's livelihood,social stability,and the construction of a Safe China.It plays an indispensable role in the comprehen-sive promotion of the rule of law.The establishment of forensic medicine as a first-level discipline,along with the transformation brought by the fifth research paradigm,makes the construction of forensic medicine stand at a new historical starting point.This paper reviews the current status and challenges of forensic medicine development,outlines the characteristics of the fifth research paradigm and its im-pact on the construction of forensic medicine,and proposes strategies for addressing these challenges.

The fluid status and rate of blood flow through the arteriovenous fistula (AVF) are two important factors affecting hemodynamic in hemodialysis patients; however, their effects on pulmonary hypertension have rarely been studied. Hence, we aimed to evaluate the effects of these factors in hemodialysis patients with pulmonary hypertension. Methods: This single-center cross-sectional survey included 219 maintenance hemodialysis patients (139 [63.5%] male). The prevalence of pulmonary hypertension was 13.6% (30 of 219). Pulmonary artery pressure was measured by echocardiography, fluid status was measured objectively using bioimpedance spectroscopy, and blood flow rate in the AVF (Qa) was determined using Doppler ultrasound. Results: The overall mean overhydration before hemodialysis was 1.5 L (range, 0.6–2.8 L). The mean overhydration in patients with and without pulmonary hypertension was 3.6 L (range, 2.3–4.6 L) and 1.4 L (range, 0.6–2.4 L), respectively (p < 0.001). The overall mean Qa was 780 mL/min (range, 570–1,015.5 mL/min). The mean Qa of patients with and without pulmonary hypertension was 672 mL/min (range, 505.7–982.2 mL/min) and 790 mL/min (range, 591–1,026 mL/min), respectively (p = 0.27). Overhydration (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.08–1.97; p = 0.01), N-terminal prohormone of brain natriuretic peptide (NT-proBNP; OR, 1.36; 95% CI, 1.09–1.71; p = 0.007), and left atrial diameter (OR, 1.14; 95% CI, 1.01–1.28; p = 0.03) were risk factors. Conclusion: Pulmonary hypertension is strongly associated with overhydration, NT-proBNP, and left atrial diameter in hemodialysis patients

Objective:To discuss the correlation between Helicobacter pylori(Hp) infection and serum 25-hydroxyvitamin D3(25(OH)D 3)level in the elderly physical examination population. Methods:It was a cross-sectional study. Selecting individuals who met the inclusion and exclusion criteria as the subjects of the study and underwent health check-ups between January 2018 and December 2019 in the Second Medical Center of Chinese PLA General Hospital.According to the Delta Over Baseline (DOB) value of 13C urea breath test, the subjects were divided into two groups: those with DOB value≥4 ( n=1 018) were diagnosed as Hp-positive and were included in the positive group, and the others were Hp-negative and were included in the negative group (DOB value<4, n=2 067). The age, gender, height, weight, disease history, family disease history and other basic medical records were recorded; and blood samples were drawn for analysis of blood test, blood biochemical test etc. Then the serum 25(OH)D 3 levels were compared between the two groups. The influencing factors of Hp infection were analyzed using a multifactor logistic regression model and the confounding factors were also adjusted. Results:A total of 3 085 elderly people (male 1 838, female 1 247) were selected in this study, the median age is 64 years, the detection rate of Hp was 33%. Single factor analysis showed that the serum 25(OH)D 3 level in the positive group was significantly lower than that in the negative group (20.59 ng/ml vs 21.07 ng/ml, P=0.012). Binary logistic regression analysis showed that the serum 25(OH)D 3 level was a negative influence factor on Hp infection( OR=0.984, P=0.008). High level of serum 25(OH)D 3 can reduce the risk of Hp infection ( OR=0.707, P=0.002). The three constructed Hp infection risk prediction models still showed statistically significant after controlling for confounding factors. Conclusion:The study shows a correlation between serum 25(OH)D 3 level and the Hp infection in the elderly people, and low level of serum 25(OH)D 3 is an independent risk factor for Hp infection in the elderly population.

Objective:To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) complicated by fatigue.Methods:COPD patients enrolled in the RealDTC study from June 2023 to March 2024 were included. Demographic data, history of acute exacerbations in the past year, smoking status, biofuel exposure, occupational exposure, modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT) score, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1)/forced vital capacity (FVC), and comorbidities (bronchial asthma, bronchiectasis, tuberculosis, cardiovascular disease, diabetes mellitus) were collected. Fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire, with a score ≤43 defined as fatigue. Patients were divided into fatigue and non-fatigue groups, and multivariate regression analysis was used to screen factors associated with fatigue in COPD patients. Results:A total of 597 COPD patients were included, of which 280(46.9%) had fatigue symptoms. Compared with non-fatigue patients, fatigue patients had lower FEV 1%pred, FEV 1/FVC, and body mass index (BMI), higher CAT and mMRC scores, and a higher proportion of occupational exposure, bronchiectasis, and treatment with long-acting β 2-agonists (LABA)/long-acting muscarinic antagonists (LAMA)/inhaled corticosteroids (ICS) (all P<0.05). Multivariate regression analysis showed that high CAT score ( OR=2.312, 95% CI: 1.366-3.911), high mMRC score ( OR=1.484, 95% CI: 1.053-2.091), occupational exposure ( OR=1.513, 95% CI: 1.082-2.116), comorbid bronchiectasis ( OR=2.452, 95% CI: 1.102-5.457), low BMI ( OR=0.935, 95% CI: 0.891-0.981), and high CAT-energy score ( OR=1.301, 95% CI: 1.149-1.473) were risk factors for fatigue in COPD patients. The CAT-energy score was highly correlated with the FACIT-F score ( r=0.260, P<0.001), and a CAT-energy score ≥2 could preliminarily screen COPD patients with fatigue. Conclusions:COPD patients with comorbid fatigue have a heavy symptom burden, are more likely to have a history of occupational exposure and bronchiectasis, and the CAT-energy score is of great reference value for screening COPD patients with fatigue.