Objective:To explore the effects of combining APR-246 with irradiation for enhancing anti-tumor immune response against 4T1 breast cancer cells, and to develop multiple tumor treatment strategies.Methods:The control group, APR-246 group, irradiation group and irradiation combined APR-246 group were used both in the cell experiment and tumor-bearing mice experiment. The inhibitory effect of APR-246 on the proliferation of 4T1 cells was assessed by using Cell Counting Kit-8. The effect of APR-246 with irradiation on the survival rate of 4T1 cells using clone formation assay was measured. The levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in tumor cells using a 2’, 7’-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe and a lipid peroxidation sensor, the tumor inhibition rates of different groups of tumor bearing mice were compared, and the proportions of CD4+ and CD8+ T cells and the ratio of M1/M2 macrophages were determined in the tumor microenvironment by flow cytometry.Results:Compared with irradiation group, 2, 4, 6 Gy irradiation combined APR-246 group significantly reduced the survival rates of 4T1 cells ( t = 2.89, 4.15, 2.62, P < 0.05), the 6 Gy irradiation combined APR-246 group significantly increased the levels of ROS ( t = 16.95, P < 0.05) and LPO ( t = 6.09, P < 0.05) in 4T1 cells, and significantly increased the apoptosis rate of 4T1 cells ( t = 10.99, P < 0.05). Meanwhile, from the 16 th day of tumor inoculation, the 10 Gy irradiation combined APR-246 group showed significantly inhibited tumor growth ( t = 2.38-2.91, P < 0.05) and significantly increased proportions of CD4+ and CD8+ T cells ( t = 9.96, 6.28, P < 0.05) and M1/M2 ratio ( t = 15.30, P < 0.05) in tumor tissues. Conclusions:APR-246 combined with irradiation can effectively increase ROS and LPO levels in 4T1 cells, promote tumor cell apoptosis, and induce anti-tumor immune response, thus potentially inhibiting the growth of 4T1 cells.

Objective:To explore the protective effects and mechanisms of an indole-3-acetaldehyde (I3A)-loaded inulin-based hydrogel against radiation-induced intestinal injury.Methods:The gelation properties and injectability of the I3A-loaded inulin-based hydrogel were detected using a rheometer, and its biocompatibility was assessed via a CCK-8 assay. Eighteen C57BL/6 mice (aged: 6-8 weeks) were stratified by body weight and randomly assigned into three groups with 6 mice in each group: blank control, irradiation-only, and irradiation+ hydrogel protection. Abdominal irradiation was administered using 137Cs γ-rays at 17 Gy. The irradiation+ hydrogel protection group received 200 μl/day of I3A-loaded inulin-based hydrogel for two days before and 2-3 days after irradiation. Meanwhile, the irradiation-only group was treated with an equivalent volume of sterile water via gavage. The mice were euthanized four days post-irradiation, and their intestinal tissues were harvested. Hematoxylin-eosin (HE) staining, Ki67 immunohistochemistry, and TUNEL immunofluorescence were performed to assess histopathological damage, epithelial cell proliferation, and apoptosis, respectively. Quantitative real-time PCR (qRT-PCR) was employed to measure mRNA levels of inflammatory and antioxidant factors. Gut microbiota composition was analyzed via 16S rRNA sequencing. Results:The test results of the rheometer confirmed successful hydrogel formation. CCK-8 assays demonstrated excellent biocompatibility. Compared with the irradiation-only group, the irradiation+ hydrogel protection group exhibited preserved intestinal histoarchitecture, a 1.5-fold increase in intestinal cell proliferation ( t = 8.35, P < 0.05), and a 2-fold reduction in radiation-induced apoptosis ( t = 7.94, P < 0.05). Moreover, the hydrogel group showed significantly elevated expression of the anti-inflammatory cytokine IL-10 and antioxidant factors NRF-2 and HO-1 ( t = 3.16, 24.83, 5.92, P < 0.05), alongside reduced levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α ( t = 5.15, 3.82, 3.83, P < 0.05). Gut microbiota analysis revealed significant modulation in microbial composition and abundance in the hydrogel group. Conclusions:The I3A-loaded inulin-based hydrogel can significantly promote intestinal cell proliferation, reduce radiation-induced apoptosis, and enhance both anti-inflammatory and antioxidant responses. In addition, it regulates gut microbiota composition and abundance, protecting against radiation-induced intestinal injury.

Objective:To investigate the effect of asiaticoside on cognitive impairment in young epileptic rats by regulating SIRT1/AMPK signaling pathway.Methods:Young rats were randomly separated into Sham group,Model group,low-dose asiaticoside(20 mg/kg)group,high-dose asiaticoside(40 mg/kg)group and high-dose asiaticoside+EX527 group.The seizure situation of rats was observed;Morris water maze was applied to test spatial learning and memory abilities;ELISA was applied to detect levels of TNF-α,IL-10,IL-6,MDA,SOD and GSH-Px in rat hippocampal tissue;Nissl staining was applied to observe morphological changes of rat hippocampal tissue;TUNEL staining was applied to detect apoptosis of hippocampal neurons in rats;Western blot was applied to detect expressions of Cleaved-caspase-3,Bax,Bcl-2,SIRT1,p-AMPK and AMPK proteins in rat hippocampal tissue.Results:Compared with Sham group,Model group showed severe tissue damage in hippocampal CA1 region of rats,epilepsy score and seizure duration were obviously increased,incubation period was obviously prolonged,levels of TNF-α,IL-6,MDA,neuronal apoptosis rate,expressions of Cleaved-caspase-3 and Bax proteins in CA1 region of hippocampus were obviously increased,the retention time and number of platform crossings were obviously decreased,levels of IL-10,SOD,GSH-Px,protein expressions of Bcl-2,SIRT1,p-AMPK/AMPK in CA1 region of hippocampus were obviously reduced(P<0.05);compared with Model group,tissue damage in hippocampal CA1 region of rats in low-dose and high-dose asiaticoside groups was obviously reduced,the epilepsy score and seizure duration were obviously decreased,incubation period was obviously shortened,levels of TNF-α,IL-6,MDA,neuronal apoptosis rate,expressions of Cleaved-caspase-3 and Bax proteins in CA1 region of hippocampus were obviously reduced,the retention time and the number of platform crossings were obviously increased,levels of IL-10,SOD,GSH-Px,protein expressions of Bcl-2,SIRT1 and p-AMPK/AMPK in CA1 region of hippocampus were obviously increased(P<0.05);EX527 was able to partially reverse the improve-ment effect of asiaticoside on epileptic young rats.Conclusion:Asiaticoside can reduce inflammatory response,oxidative stress and hippocampal neuronal apoptosis in rats and reduce nerve damage by activating SIRT1/AMPK signaling pathway,thus improving cogni-tive function of young epileptic.

Objective:To investigate the effect of asiaticoside on cognitive impairment in young epileptic rats by regulating SIRT1/AMPK signaling pathway.Methods:Young rats were randomly separated into Sham group,Model group,low-dose asiaticoside(20 mg/kg)group,high-dose asiaticoside(40 mg/kg)group and high-dose asiaticoside+EX527 group.The seizure situation of rats was observed;Morris water maze was applied to test spatial learning and memory abilities;ELISA was applied to detect levels of TNF-α,IL-10,IL-6,MDA,SOD and GSH-Px in rat hippocampal tissue;Nissl staining was applied to observe morphological changes of rat hippocampal tissue;TUNEL staining was applied to detect apoptosis of hippocampal neurons in rats;Western blot was applied to detect expressions of Cleaved-caspase-3,Bax,Bcl-2,SIRT1,p-AMPK and AMPK proteins in rat hippocampal tissue.Results:Compared with Sham group,Model group showed severe tissue damage in hippocampal CA1 region of rats,epilepsy score and seizure duration were obviously increased,incubation period was obviously prolonged,levels of TNF-α,IL-6,MDA,neuronal apoptosis rate,expressions of Cleaved-caspase-3 and Bax proteins in CA1 region of hippocampus were obviously increased,the retention time and number of platform crossings were obviously decreased,levels of IL-10,SOD,GSH-Px,protein expressions of Bcl-2,SIRT1,p-AMPK/AMPK in CA1 region of hippocampus were obviously reduced(P<0.05);compared with Model group,tissue damage in hippocampal CA1 region of rats in low-dose and high-dose asiaticoside groups was obviously reduced,the epilepsy score and seizure duration were obviously decreased,incubation period was obviously shortened,levels of TNF-α,IL-6,MDA,neuronal apoptosis rate,expressions of Cleaved-caspase-3 and Bax proteins in CA1 region of hippocampus were obviously reduced,the retention time and the number of platform crossings were obviously increased,levels of IL-10,SOD,GSH-Px,protein expressions of Bcl-2,SIRT1 and p-AMPK/AMPK in CA1 region of hippocampus were obviously increased(P<0.05);EX527 was able to partially reverse the improve-ment effect of asiaticoside on epileptic young rats.Conclusion:Asiaticoside can reduce inflammatory response,oxidative stress and hippocampal neuronal apoptosis in rats and reduce nerve damage by activating SIRT1/AMPK signaling pathway,thus improving cogni-tive function of young epileptic.

Objective: To explore the correlation between the composition of bone marrow lymphocyte subsets and the clinical attributes observed in de novo AML patients, as well as their influence on prognosis. Methods: A detailed study was carried out on a cohort of 191 de novo acute myeloid leukemia patients who were admitted to our medical center between October 2022 and September 2024. In addition, a group of 24 patients with iron deficiency anemia individuals was carefully chosen as the control cohort. The proportions of lymphocyte subsets within the bone marrow of de novo AML patients were analyzed. Furthermore, an in-depth analysis was performed to investigate the association between the expression levels of these subsets in de novo AML patients and their clinical attributes, as well as their prognostic implications. Results: The proportion of CD19 and CD56 lymphocytes within the bone marrow of de novo AML patients significantly diminished compared to the control cohort (8.5% vs 13.2% P<0.05, and 15.5% vs 18.0%, P<0.05). Conversely, no significant discrepancies were observed in the CD3 , CD3 CD4 , and CD3 CD8 lymphocyte percentages between the AML patients and control group (71.7% vs 72.1%, 32.5% vs 33.7% and 32.8% vs 35.7%, P>0.05). When analyzing the relationships between lymphocyte subsets within the bone marrow of de novo patients and their respective clinical characteristics, patients aged 60 years and above exhibited diminished percentages of CD3 CD8 lymphocytes in the bone marrow compared to their younger counterparts (31.6% vs 34.1%, P<0.05), while the CD56 lymphocyte subsets demonstrated an increased prevalence (17.2% vs 14.4%, P<0.05). Furthermore, patients with leukocytosis (WBC≥100×10 /L) presented lower levels of CD3 and CD3 CD4 lymphocytes in the bone marrow compared with those without it (65.3% vs 72.9% P<0.05, and 28.9% vs 33.2%, P<0.05), respectively. The AML1-ETO fusion gene-positive cohort exhibited a higher prevalence of CD3 CD8 lymphocytes in the bone marrow than in the negative group (38.2% vs 32.3%, P<0.05), whereas the FLT3-ITD mutation-positive group presented a decreased prevalence of CD56 lymphocytes compared with the negative group (12.4% vs 16.8%, P<0.05). In addition, the NPM1 mutation-positive group demonstrated lower levels of CD3 CD8 lymphocytes in the bone marrow than in the negative group (29.1% vs 33.3%, P<0.05). Variables such as tumor protein p53(TP53) mutation positive, the absence of hematopoietic stem cell transplantation, and CD3 CD4 lymphocyte proportions below 25% were identified as independent adverse prognostic indicators for AML patients (P<0.05). Conclusion: The pathogenesis of AML is closely associated with an imbalance in bone marrow lymphocyte subsets. The FLT3-ITD mutation potentially contributes to the dysregulation of CD56 lymphocyte subset expression. The AML1-ETO fusion gene and NPM1 mutation are implicated in the abnormal expression of CD3 CD8 lymphocytes within the bone marrow. Moreover, the percentage of CD3 CD4 lymphocytes in the bone marrow serves as a prognostic factor for de novo AML patients.

Objective: To explore the correlation between the composition of bone marrow lymphocyte subsets and the clinical attributes observed in de novo AML patients, as well as their influence on prognosis. Methods: A detailed study was carried out on a cohort of 191 de novo acute myeloid leukemia patients who were admitted to our medical center between October 2022 and September 2024. In addition, a group of 24 patients with iron deficiency anemia individuals was carefully chosen as the control cohort. The proportions of lymphocyte subsets within the bone marrow of de novo AML patients were analyzed. Furthermore, an in-depth analysis was performed to investigate the association between the expression levels of these subsets in de novo AML patients and their clinical attributes, as well as their prognostic implications. Results: The proportion of CD19 and CD56 lymphocytes within the bone marrow of de novo AML patients significantly diminished compared to the control cohort (8.5% vs 13.2% P<0.05, and 15.5% vs 18.0%, P<0.05). Conversely, no significant discrepancies were observed in the CD3 , CD3 CD4 , and CD3 CD8 lymphocyte percentages between the AML patients and control group (71.7% vs 72.1%, 32.5% vs 33.7% and 32.8% vs 35.7%, P>0.05). When analyzing the relationships between lymphocyte subsets within the bone marrow of de novo patients and their respective clinical characteristics, patients aged 60 years and above exhibited diminished percentages of CD3 CD8 lymphocytes in the bone marrow compared to their younger counterparts (31.6% vs 34.1%, P<0.05), while the CD56 lymphocyte subsets demonstrated an increased prevalence (17.2% vs 14.4%, P<0.05). Furthermore, patients with leukocytosis (WBC≥100×10 /L) presented lower levels of CD3 and CD3 CD4 lymphocytes in the bone marrow compared with those without it (65.3% vs 72.9% P<0.05, and 28.9% vs 33.2%, P<0.05), respectively. The AML1-ETO fusion gene-positive cohort exhibited a higher prevalence of CD3 CD8 lymphocytes in the bone marrow than in the negative group (38.2% vs 32.3%, P<0.05), whereas the FLT3-ITD mutation-positive group presented a decreased prevalence of CD56 lymphocytes compared with the negative group (12.4% vs 16.8%, P<0.05). In addition, the NPM1 mutation-positive group demonstrated lower levels of CD3 CD8 lymphocytes in the bone marrow than in the negative group (29.1% vs 33.3%, P<0.05). Variables such as tumor protein p53(TP53) mutation positive, the absence of hematopoietic stem cell transplantation, and CD3 CD4 lymphocyte proportions below 25% were identified as independent adverse prognostic indicators for AML patients (P<0.05). Conclusion: The pathogenesis of AML is closely associated with an imbalance in bone marrow lymphocyte subsets. The FLT3-ITD mutation potentially contributes to the dysregulation of CD56 lymphocyte subset expression. The AML1-ETO fusion gene and NPM1 mutation are implicated in the abnormal expression of CD3 CD8 lymphocytes within the bone marrow. Moreover, the percentage of CD3 CD4 lymphocytes in the bone marrow serves as a prognostic factor for de novo AML patients.

Objective:To explore the effects of combining APR-246 with irradiation for enhancing anti-tumor immune response against 4T1 breast cancer cells, and to develop multiple tumor treatment strategies.Methods:The control group, APR-246 group, irradiation group and irradiation combined APR-246 group were used both in the cell experiment and tumor-bearing mice experiment. The inhibitory effect of APR-246 on the proliferation of 4T1 cells was assessed by using Cell Counting Kit-8. The effect of APR-246 with irradiation on the survival rate of 4T1 cells using clone formation assay was measured. The levels of reactive oxygen species (ROS) and lipid peroxidation (LPO) in tumor cells using a 2’, 7’-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe and a lipid peroxidation sensor, the tumor inhibition rates of different groups of tumor bearing mice were compared, and the proportions of CD4+ and CD8+ T cells and the ratio of M1/M2 macrophages were determined in the tumor microenvironment by flow cytometry.Results:Compared with irradiation group, 2, 4, 6 Gy irradiation combined APR-246 group significantly reduced the survival rates of 4T1 cells ( t = 2.89, 4.15, 2.62, P < 0.05), the 6 Gy irradiation combined APR-246 group significantly increased the levels of ROS ( t = 16.95, P < 0.05) and LPO ( t = 6.09, P < 0.05) in 4T1 cells, and significantly increased the apoptosis rate of 4T1 cells ( t = 10.99, P < 0.05). Meanwhile, from the 16 th day of tumor inoculation, the 10 Gy irradiation combined APR-246 group showed significantly inhibited tumor growth ( t = 2.38-2.91, P < 0.05) and significantly increased proportions of CD4+ and CD8+ T cells ( t = 9.96, 6.28, P < 0.05) and M1/M2 ratio ( t = 15.30, P < 0.05) in tumor tissues. Conclusions:APR-246 combined with irradiation can effectively increase ROS and LPO levels in 4T1 cells, promote tumor cell apoptosis, and induce anti-tumor immune response, thus potentially inhibiting the growth of 4T1 cells.

Objective:To explore the protective effects and mechanisms of an indole-3-acetaldehyde (I3A)-loaded inulin-based hydrogel against radiation-induced intestinal injury.Methods:The gelation properties and injectability of the I3A-loaded inulin-based hydrogel were detected using a rheometer, and its biocompatibility was assessed via a CCK-8 assay. Eighteen C57BL/6 mice (aged: 6-8 weeks) were stratified by body weight and randomly assigned into three groups with 6 mice in each group: blank control, irradiation-only, and irradiation+ hydrogel protection. Abdominal irradiation was administered using 137Cs γ-rays at 17 Gy. The irradiation+ hydrogel protection group received 200 μl/day of I3A-loaded inulin-based hydrogel for two days before and 2-3 days after irradiation. Meanwhile, the irradiation-only group was treated with an equivalent volume of sterile water via gavage. The mice were euthanized four days post-irradiation, and their intestinal tissues were harvested. Hematoxylin-eosin (HE) staining, Ki67 immunohistochemistry, and TUNEL immunofluorescence were performed to assess histopathological damage, epithelial cell proliferation, and apoptosis, respectively. Quantitative real-time PCR (qRT-PCR) was employed to measure mRNA levels of inflammatory and antioxidant factors. Gut microbiota composition was analyzed via 16S rRNA sequencing. Results:The test results of the rheometer confirmed successful hydrogel formation. CCK-8 assays demonstrated excellent biocompatibility. Compared with the irradiation-only group, the irradiation+ hydrogel protection group exhibited preserved intestinal histoarchitecture, a 1.5-fold increase in intestinal cell proliferation ( t = 8.35, P < 0.05), and a 2-fold reduction in radiation-induced apoptosis ( t = 7.94, P < 0.05). Moreover, the hydrogel group showed significantly elevated expression of the anti-inflammatory cytokine IL-10 and antioxidant factors NRF-2 and HO-1 ( t = 3.16, 24.83, 5.92, P < 0.05), alongside reduced levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α ( t = 5.15, 3.82, 3.83, P < 0.05). Gut microbiota analysis revealed significant modulation in microbial composition and abundance in the hydrogel group. Conclusions:The I3A-loaded inulin-based hydrogel can significantly promote intestinal cell proliferation, reduce radiation-induced apoptosis, and enhance both anti-inflammatory and antioxidant responses. In addition, it regulates gut microbiota composition and abundance, protecting against radiation-induced intestinal injury.

Objective The objective of this study was to investigate a risk of prostate cancer(PCa) at a repeat biopsy in patients with chronic prostate inflammation and widespread high grade prostatic intra epithelial neoplasia(wHGPIN).Methods From July 2006 to December 2014,172 cases of prostate biopsy were collected.All of them were diagnosed as HGPIN for the first biopsy,punctured by transrectal ultrasound for 12 points.After the first puncture for 6 months,patients were punctured for rebiopsy.Multi-focal wHGPIN was defined as a high -grade prostate intraepithelial neoplasia with 2 or more cores detection in a prostate biopsy.Isolated HGPIN was defined as a high-grade prostate intraepithelial neoplasia with only one core detection in a prostate biopsy.Results Seventy-two patients with HGPIN were isolated from primary HGPIN,102 patients with isolated HGPIN,17 patients with chronic prostatitis,70 with multifocal HGPIN and 54 with chronic prostatitis.Forth-eight of 172 patients initial diagnosis of HGPIN was diagnosed as PCa at rebiopsy.The detection rate of wHGPIN was 52.86％ (37/70)and isolated HGPIN for 10.88％ (11/102).They showed a statistically difference between two groups(P ＜0.001).The detection rate of PCa in HGPIN patients with chronic prostatitis was higher than that in patients without chronic prostatitis(P =0.011).Chronic prostatitis and multifocal wHGPIN were a risk factor for prostate cancer independent by rebiopsy,confirmed by the logistic regression model.Conclusion Rebiopsy is a high risk factor of prostate adenocarcinoma for patients with chronic prostatitis and multifocal HGPIN initially diagnosed by the first biopsy.Therefore,these patients are recommended under ultrasound induced by rectal prostate rebiopsy.

Objective To investigate application effect of micro-courses in the clinical teaching of operating room nursing , and to improve practice quality .Methods A total of 81 nursing interns of Grade 2012, majored in Nursing of Cangzhou Medical College , had internship from July 2014 to November 2014 were treated as the control group;another 82 nursing interns , who had internship from December 2014 to April 2015 were treated as the observation group .The control group applied traditional one-one teaching style , while observation group used an extra operating room nursing micro curriculum on this basis .At the end of the operating room practice , theory, skills assessment , self-satisfaction and satisfaction of teaching methods were compared.Results Observation group theory and skills assessment scores were better than the control group [(83.72 ±3.53) vs (71.21 ±4.36), (89.72 ±3.53) vs (81.21 ±4.36);t=14.58, 11.15;P<0.01)]. nursing interns self-learning satisfaction of the control group and the observation group were 88.9% and 98.8%respectively(Z=12.73, P<0.01).Nursing interns teaching methods satisfaction for operating room teaching of the control group and the observation group were 90.1% and 100.0% respectively ( Z=17.12, P<0.01).Conclusions During clinical teaching of operating room nursing , micro courses could improve the quality of practice , improve nursing interns′self-study and clinical teaching satisfaction .