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.

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

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.

Objective This study aims to analyze the factors influencing per capita current health expenditure in Guizhou Province from 2016 to 2022 using the gray correlation analysis method.Methods Based on the"SHA2011"accounting results of current health expenditure in Guizhou Province,as well as data from the"Guizhou Statistical Yearbook"and"Guizhou Health Statistical Yearbook",the gray correlation analysis method was used to analyze the factors influencing per capita current health expenditure in Guizhou Province from 2016 to 2022.Results The factors with the highest correlation to per capita current health expenditure in Guizhou Province were health expenditure(0.829),followed by the number of health technical personnel per thousand people(0.715),the number of practicing(assistant)physicians per thousand people(0.705),and per capita GDP(0.704).The factor with the lowest correlation was the proportion of the tertiary industry to GDP(0.543).Conclusion Health expenditure investment has the strongest correlation with per capita current health expenditure in Guizhou Province.Health re-source investment and health service capacity are the main influencing factors of per capita current health expenditure in Guizhou Province.At the same time,the impact of economic and social factors on current health expenditure should be fully recognized.

Objective To evaluate the effects of fasting and high-fat diet on the pharmacokinetics of rabeprazole sodium enteric-coated tablets in healthy Chinese subjects.Methods A single-center,randomized,open,two-agent,two-sequence,four-cycle,fully repeated crossover,single-dose trial design was used in this study,healthy subjects were assigned to receive single dose of rabeprazole sodium enteric-coated tablets 0.1 g in either fasting or high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of rabeprazole sodium enteric-coated in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),the model method of the non-compartmental was used to calculate the pharmacokinetic parameters by Phoenix WinNonlin 8.2.Results The main pharmacokinetic parameters of rabeprazole sodium enteric-coated tablets in fasting state and high-fat diet state were as follows:Cmax were(339.63±156.47)and(318.86±132.13)ng·mL-1;t1/2 were(2.34±0.68)and(3.60±2.40)h;AUC0_t were(556.62±251.65)and(528.50±201.78)ng·mL-1·h;AUC0-∞ were(563.39±255.69)and(535.15±203.24)ng·mL-1·h;tmax were 3.65 and 6.99 h.After high-fat diet,the Cmax and AUC of rapeprazole sodium after high-fat and high-calorie diet decreased,Cmax decreased by 6.12％,AUC0-t decreased by 5.05％,AUC0-∞ decreased by 5.01％,andtmaxwas delayed by about 3.34 h.Cmax,AUC0-t and AUC0-∞ 90％confidence interval were 73.13％-115.10％,83.22％-112.28％and 83.40％-112.13％,respectively.Neither was between 85.00％-125.00％.Conclusion High-fat diet affects the absorption rate and degree of rabeprazole sodium enteric-coated,so it is suitable to be administered on an empty stomach.