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 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.

Objective:To investigate the efficacy of Saussurea involucrata injection (SII) in alleviating rheumatoid arthritis (RA) and to explore the mechanism of action of SII in alleviating RA through the Toll-like receptor 4 (TLR4)/nuclear factor-kappaBp65 (NF-κBp65) pathway-mediated M1 macrophage polarization.Methods:In vivo experiments were conducted using a collagen-induced arthritis (CIA) rat model. After successful modeling, the CIA rats were randomly assigned into five groups ( n=10 per group): CIA control group, MTX group, low-dose SII (L-SII) group, medium-dose SII (M-SII) group, and high-dose SII (H-SII) group. The efficacy of SII in alleviating RA was evaluated using arthritis index scores, histopathology, and ELISA to measure serum levels of nitric oxide (NO), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Subsequently, Western blot analysis was used to detect the expression of inducible nitric oxide synthase (iNOS) and CD86 proteins in synovial tissue. In vitro experiments involved first isolating and inducing rat bone marrow-derived macrophages (BMDMs). Then, BMDMs were polarized toward the M1 phenotype using lipopolysaccharide (LPS) combined with interferon-γ (IFN-γ). Concurrently, cells were treated with SII and the TLR4 inhibitor TAK242. Subsequently, ELISA was used to detect NO, IL-1β, TNF-α levels in the cell culture supernatant via ELISA. RT-qPCR was used to detect the expression of IL-1b, IL-6, and TNF-α genes in each group of cells. Western blot analysis was performed to detect the expression of iNOS, CD86, TLR4, myeloid differentiation primary response 88 (MyD88), and p-NF-κBp65/NF-κBp65 proteins in the cells. Data analysis between multiple groups was performed using one-way analysis of variance, and between pairs using LSD- t-tests. Results:In vivo experimental results showed that compared with the CIA group(7.90 ± 0.70), MTX and SII both improved the pathological symptoms of rats and reduced the ankle joint pathological score [MTX (4.40 ± 0.92), L-SII (7.00 ± 0.89), M-SII (5.10 ± 1.30), H-SII (4.90 ± 0.94), t=33.86, P<0.001; t=9.10, P<0.001; t=2.38, P=0.029; t=5.69, P<0.001; t=7.66, P<0.001], while downregulating serum levels of NO, IL-1β, IL-6, and TNF-α levels in serum, as well as iNOS [ t=30.01, P<0.001; t=6.17, P=0.003; t=10.86, P<0.001; t=28.95, P<0.001; t=19.03, P<0.001] and CD86 [ t=65.61, P<0.001; t=8.76, P<0.001; t=13.18, P<0.001; t=13.22, P<0.001; t=18.91, P<0.001] expression. In vitro experimental results showed that compared with BMDMs treated with LPS and IFN-γ, SII and TAK242 treatment reduced the levels of NO, IL-1β, IL-6, and TNF-α in the supernatant and decreased the expression of IL-1b, IL-6, and TNF-α genes. Additionally, SII and TAK242 treatment downregulated the expression of iNOS and CD86 proteins in cells, and simultaneously downregulated TLR4, MYD88, and p-NF-κBp65/NF-κBp65 expression ( t=35.84, P<0.001; t=15.69, P<0.001; t=21.99, P<0.001; t=23.64, P<0.001; t=22.50, P<0.001). Additionally, compared with the TAK242 group alone, TAK242 + H-SII showed no significant differences in the modulation of M1 macrophage polarization and TLR4/NF-κBp65 pathway-related indicators. Conclusion:SII exerts anti-inflammatory and anti-RA effects by inhibiting TLR4/NF-κBp65-mediated M1 macrophage polarization.

Objective:To investigate the predictive value of measured cardiac power output(CPO)of echocardiography for the prognosis of elderly patients with acute heart failure(AHF)in the vulnerable period of heart failure.Methods:A total of 120 elderly patients with AHF who admitted to the Third Hospital Affiliated to Shanxi Medical University from January 2021 to January 2024 were selected,and they were divided into the major adverse cardiovascular events(MACE)group(18 cases)and the non-MACE group(102 cases)according to whether occurred MACE in the vulnerable period within 3 months after discharge.The baseline data of the two groups of patients were compared.Logistic regression was used to analyze the influencing factors of occurring MACE in the vulnerable period of patients,and the receiver operating characteristic(ROC)curve was used to analyze the predictive value of CPO for MACE in the vulnerable period of heart failure in elderly patients with AHF.Results:In the baseline data of patients,the total cholesterol,25-hydroxyvitamin D[25(OH)D],reserve CPO,resting CPO,and peak CPO in the MACE group were all lower than those in the non-MACE group,and the differences were statistically significant(t=5.987,2.236,2.921,2.390,4.569,P<0.05).The levels of brain natriuretic peptide(BNP)and N-terminal pro-brain natriuretic peptide(NT-proBNP)in the MACE group were higher than those in the non-MACE group,and the differences were statistically significant(t=22.074,23.368,P<0.05).The results of Logistic regression analysis showed that the total cholesterol,25(OH)D,reserve CPO,resting CPO,and peak CPO were all influencing factors for the occurrence of MACE during the vulnerable period of heart failure in patients(OR=0.064,0.942,0.015,0.035,0.041,P<0.05).ROC curve analysis showed that the efficacy of resting CPO and reserve CPO of the cardiac function indicators in predicting MACE of patients were slightly lower than that of peak CPO.The AUC,sensitivity and specificity of peak CPO in predicting MACE of patients were 0.752,92.2%and 55.6%,respectively.Conclusion:The lower peak CPO value of cardiac function indicator of echocardiography is independent risk factor for MACE during the vulnerable period of heart failure in elderly patients with AHF.Measuring CPO can identify potential poor prognosis populations in advance.

Military training represents one of the most essential activities for troops during peacetime,of which the prevention and treatment of training-induced injuries are a very important part.Recent findings of research suggest that cold atmospheric plasma(CAP)exhibits a distinctive and multifaceted superiority in terms of broad-spectrum sterilization,rapid blood coagulation and healing promotion for wounds.Consequently,CAP has good prospects of applications in diverse fields such as clinical medicine,emergency rescue and military medicine.Based on a review of the research progress in plasma medicine,the applicability of CAP in the prevention and treatment of military training injuries was discussed in this paper by focusing on the urgent issues related to military training injury,including the typical application scenarios and methods for CAP,the safety and effectiveness of plasma trauma prevention and treatment,and the key issues facing the prevention and treatment of military training injuries.

Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.

Objective To explore the predictive value of automated breast ultrasound(ABUS)features combined with Ki-67 in predicting pathological complete response(pCR)after neoadjuvant chemotherapy(NAC)in triple-negative breast cancer(TNBC).Methods A retrospective analysis was conducted on 127 female TNBC patients treated at Xijing Hospital,Air Force Medical University from March 2019 to December 2023.All patients underwent NAC and surgical treatment after ABUS examination.Based on postoperative pathological results,patients were divided into pCR group(n=60)and non-pathological complete response(npCR)group(n=67).Differences in various parameters before NAC were compared between the two groups.LASSO regression was used to identify independent factors influencing pCR after NAC in TNBC patients,and a predictive model was constructed using multivariate logistic regression.The prediction model was internally validated using the Bootstrap method(1000 resamples).The discriminative ability of the model was evaluated using receiver operating characteristic(ROC)curves,and the area under the curves(AUCs)of different prediction models were compared using De-long's test.The accuracy of the model was assessed using calibration curves,and the clinical benefit of the model was evaluated using clinical decision curve analysis(DCA).Results Significant differences were observed between two groups in terms of age,Ki-67,menopausal status,tumor type,posterior echo,coronal plane convergence sign,coronal plane skip sign,and coronal plane white wall sign before NAC(P<0.05).LASSO regression analysis showed that Ki-67,coronal plane convergence sign,and coronal plane white wall sign were independent influencing factors of pCR after NAC in TNBC patients(P<0.05).The AUC of the multivariate logistic regression model based on Ki-67 was 0.733(95%CI 0.646-0.819),the AUC of ABUS model was 0.777(95%CI 0.695-0.858),and the AUC of ABUS combined with Ki-67 model was 0.816(95%CI 0.741-0.890).De-long's test showed that the AUC of the combined model was higher than those of ABUS feature model and Ki-67 model,with statistically significant differences(P<0.05).There was no significant difference in the AUC between ABUS feature model and Ki-67 model(P=0.40).Hosmer-Lemeshow test indicated that the combined model had a good fit(P=0.304).Internal validation results showed that the combined model had a good stability with a consistency index(C-index)of 0.820(95%CI 0.726-0.879).The calibration curve demonstrated good consistency between the predicted and actual probabilities of the combined prediction model,and the DCA curve indicated that the model had favorable clinical benefit.Conclusion The combined ABUS feature and Ki-67 model can be used to predict the probability of pCR after NAC in TNBC patients,providing a reference for the formulation of clinical treatment plans in TNBC patients.

BACKGROUND: Both medication and non-medication therapies are effective approaches to control blood pressure (BP) in hypertension patients. However, the association of joint changes in antihypertensive medication use and healthy lifestyle index (HLI) with BP control among hypertension patients is seldom reported, which needs to provide more evidence by prospective intervention studies. We examined the association of antihypertensive medication use and HLI with BP control among employees with hypertension in China based on a workplace-based multicomponent intervention program. METHODS: Between January 2013 and December 2014, a cluster randomized clinical trial of a workplace-based multicomponent intervention program was conducted in 60 workplaces across 20 urban areas in China. Workplaces were randomly divided into intervention (n = 40) and control (n = 20) groups. Basic information on employees at each workplace was collected by trained professionals, including sociodemographic characteristics, medical history, family history, lifestyle behaviors, medication status and physical measurements. After baseline, the intervention group received a 2-year intervention to achieve BP control, which included: (1) a workplace wellness program for all employees; (2) a guidelines-oriented hypertension management protocol. HLI including nonsmoking, nondrinking, adequate physical activity, weight within reference range and balanced diet, were coded on a 5-point scale (range: 0-5, with higher score indicating a healthier lifestyle). Antihypertensive medication use was defined as taking drug within the last 2 weeks. Changes in HLI, antihypertensive medication use and BP control from baseline to 24 months were measured after the intervention. RESULTS: Overall, 4655 employees were included (age: 46.3 ± 7.6 years, men: 3547 (82.3%)). After 24 months of the intervention, there was a significant improvement in lifestyle [smoking (OR = 0.65, 95% CI: 0.43-0.99; P = 0.045), drinking (OR = 0.52, 95% CI: 0.40-0.68; P < 0.001), regular exercise (OR = 3.10, 95% CI: 2.53-3.78; P < 0.001), excessive intake of fatty food (OR = 0.17, 95% CI: 0.06-0.52; P = 0.002), restrictive use of salt (OR = 0.26, 95% CI: 0.12-0.56; P = 0.001)]. Compare to employees with a deteriorating lifestyle after the intervention, those with an improved lifestyle had a higher BP control. In the intervention group, compared with employees not using antihypertensive medication, those who consistent used (OR = 2.34; 95% CI: 1.16-4.72; P = 0.017) or changed from not using to using antihypertensive medication (OR = 2.24; 95% CI: 1.08-4.62; P = 0.030) had higher BP control. Compared with those having lower HLI, participants with a same (OR = 1.38; 95% CI: 0.99-1.93; P = 0.056) or high (OR = 1.79; 95% CI: 1.27~2.53; P < 0.001) HLI had higher BP control. Those who used antihypertensive medication and had a high HLI had the highest BP control (OR = 1.88; 95% CI: 1.32-2.67, P < 0.001). Subgroup analysis also showed the consistent effect as the above. CONCLUSION These findings suggest that adherence to antihypertensive medication treatment and healthy lifestyle were associated with a significant improvement in BP control among employees with hypertension.

Progressive symmetric erythrokeratodermia(PSEK)is a rare hereditary skin disease charac-terized by symmetrical erythema,hyperkeratosis and multiorgan lesions.Its clinical phenotypes are highly heterogeneous and may be accompanied by symptoms such as thrombocytopenia,which can be fatal in se-vere cases.The genotype-phenotype association mechanism of PSEK is extremely complex.Currently,it is known that mutations in multiple genes such as GJB3,KDSR,and KRT83 can cause the disease.A-mong them,3-ketodihydrosphingosine reductase(KDSR)has been found to harbor nearly 20 clinical mu-tations.These mutations interfere with the de novo ceramide synthesis pathway,disrupt the homeostasis of the skin barrier,and cause platelet production disorders and multi-organ lesions,making it a current research hotspot in the molecular mechanism of PSEK.The pathogenic mutations of KDSR are widely and uniformly distributed throughout the entire protein,rather than being limited to the traditionally recog-nized active center,suggesting that the impairment of the KDSR enzymatic activity is not the only cause of PSEK.In view of this,this study selected four typical mutants of KDSR(KDSRQG55-56R,KDSRn38C,KDSRY186F,KDSRG182S),and first used recombinant expression technology to prepare pure and homoge-neous mutant proteins.Subsequently,thermal stability experiments as well as oligomerization analysis were conducted on these four mutant proteins.The results showed that the Tm values of the four mutants were significantly lower than that of the wild type.Particularly,KDSRF138C and KDSRQG55-56R were nearly completely denatured at physiological temperature.This result was perfectly consistent with the further Rosetta energy analysis.In conclusion,this study took several pathological mutations of the PSEK patho-genic factor KDSR as the research object and discovered that the conformational stability of KDSR might be closely related to the occurrence of PSEK pathogenicity,indicating that the imbalance of conformation-al homeostasis is very likely to be one of the common contributing factors of many genetic diseases,inclu-ding PSEK.This provides a new theoretical basis and reference for explaining the molecular mechanism of genotype-phenotype heterogeneity in many genetic diseases.