Pancreatic cancer has emerged as one of the most challenging malignancies worldwide,with its high resistance to chemotherapy being the primary cause of treatment failure.Therefore,enhancing the chemosensitivity of pancreatic cancer has become a major focus of current research.In this study,we in-vestigated how Bufotaline,a bufadienolide extracted from the traditional Chinese medicine toad venom,exhibits its antitumor activity.Specifically,we explored the potential of Bufotaline to enhance the chemo-sensitivity of pancreatic cancer cells to Adriamycin and elucidated its underlying molecular mechanisms.Using CCK-8 and colony formation assays,we demonstrated that Bufotaline enhances the inhibitory effect of Adriamycin on the survival of pancreatic cancer cell lines Patu-8988T,Aspc-1,and Patu-8988S.No-tably,Bufotaline treatment reduced the IC50 of Adriamycin in drug-resistant pancreatic cancer cells to lev-els comparable to those in non-resistant cells.Results from Western blot,immunofluorescence,comet as-say,and TUNEL assays revealed that Bufotaline promotes Adriamycin-induced DNA damage in pancreatic cancer cells.RNA-seq analysis of Patu-8988T cells treated with Adriamycin alone or in combination with Bufotaline showed significant changes in gene expression,and qRT-PCR analysis further confirmed that Bu-fotaline downregulates the expression of DNA damage repair proteins NBS1 and RAD50.Moreover,Western blot analysis revealed that Bufotaline reduces the levels of DNA damage response repair proteins,and Im-munofluorescence experiments indicated that Bufotaline inhibits the activation of the ATM/CHK2 signaling pathway.Finally,in a subcutaneous xenograft mouse model,the combination of Adriamycin and Bufotaline treatment significantly suppressed pancreatic cancer cell growth.In conclusion,Bufotaline enhances Adria-mycin-induced chemosensitivity in pancreatic cancer cells;the combination of Adriamycin and Bufotaline downregulates the expression of DNA damage response repair proteins NBS1 and RAD50,and inhibits the ATM/CHK2-mediated DDR signaling pathway,thereby delaying DNA damage repair.

Pancreatic cancer has emerged as one of the most challenging malignancies worldwide,with its high resistance to chemotherapy being the primary cause of treatment failure.Therefore,enhancing the chemosensitivity of pancreatic cancer has become a major focus of current research.In this study,we in-vestigated how Bufotaline,a bufadienolide extracted from the traditional Chinese medicine toad venom,exhibits its antitumor activity.Specifically,we explored the potential of Bufotaline to enhance the chemo-sensitivity of pancreatic cancer cells to Adriamycin and elucidated its underlying molecular mechanisms.Using CCK-8 and colony formation assays,we demonstrated that Bufotaline enhances the inhibitory effect of Adriamycin on the survival of pancreatic cancer cell lines Patu-8988T,Aspc-1,and Patu-8988S.No-tably,Bufotaline treatment reduced the IC50 of Adriamycin in drug-resistant pancreatic cancer cells to lev-els comparable to those in non-resistant cells.Results from Western blot,immunofluorescence,comet as-say,and TUNEL assays revealed that Bufotaline promotes Adriamycin-induced DNA damage in pancreatic cancer cells.RNA-seq analysis of Patu-8988T cells treated with Adriamycin alone or in combination with Bufotaline showed significant changes in gene expression,and qRT-PCR analysis further confirmed that Bu-fotaline downregulates the expression of DNA damage repair proteins NBS1 and RAD50.Moreover,Western blot analysis revealed that Bufotaline reduces the levels of DNA damage response repair proteins,and Im-munofluorescence experiments indicated that Bufotaline inhibits the activation of the ATM/CHK2 signaling pathway.Finally,in a subcutaneous xenograft mouse model,the combination of Adriamycin and Bufotaline treatment significantly suppressed pancreatic cancer cell growth.In conclusion,Bufotaline enhances Adria-mycin-induced chemosensitivity in pancreatic cancer cells;the combination of Adriamycin and Bufotaline downregulates the expression of DNA damage response repair proteins NBS1 and RAD50,and inhibits the ATM/CHK2-mediated DDR signaling pathway,thereby delaying DNA damage repair.

ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Objective:To investigate mental health literacy and advance care planning(ACP)condition,their influencing fac-tors,and their correlation in elderly patients with coronary heart disease(CHD).Methods:General data of 500 elderly CHD patients admitted in the Second Affiliated Hospital of Chinese PLA Air Force Military Medical University between January 2020 and December 2021 were collected.Mental health literacy and ACP condition were assessed.Multivariate linear regres-sion was used to analyze their influencing factors,and Pearson method was used to analyze their association.Results:Total score of Multicomponent Mental Health Literacy(MHL)was(10.78±2.57)points,and total score of Advance Care Plan-ning Readiness Scale(ACPRS)was(71.41±4.84)points in the 500 elderly CHD patients.Multivariate linear regression a-nalysis indicated that level of disease uncertainty had negative impact on MHL score,presence of spouse and trust in medical care had positive impact on MHL score(P＜0.05 or＜0.01);number of complications had negative impact on ACPR score,while presence of spouse and family mean monthly income had positive impact on ACPRS score(P＜0.05 or＜0.01).Pearson correlation analysis indicated that MHL score was positively correlated with ACPRS score(r=0.476,P＜0.001).Conclusion:Both mental health literacy and ACP status need to be improved in elderly CHD patients.They are posi-tively correlated with each other.Presence of spouse,number of complications and trust in medical care are the important influencing factors.Therefore,medical staff can take targeted measures to improve ACP readiness and mental health quality.

Objective:This study aims to explore the rehabilitation effect of continuous rehabilitation management based on Internet thinking on patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:This randomized controlled study enrolled 100 CHD patients admitted in Second Affiliated Hospi-tal of Chinese PLA Air Force Military Medical University between October 2020 and December 2021.They were di-vided into control group(n=50)and intervention group(n=50).Patients in control group received routine reha-bilitation nursing mode,compared to those in intervention group applying"Internet+"continuous rehabilitation nursing intervention program,both groups were intervened for 3 months.Cardiac function,cardiopulmonary exer-cise test indexes,depression,medication compliance,quality of life and incidence of adverse cardiovascular events within 1-year follow-up were compared between two groups.Results:Compared with patients in control group after 3 months,those in intervention group had significant higher oxygen uptake at anaerobic threshold(VO2@AT)[(11.75±0.39)ml·kg-1·min-1 vs.(10.17±0.76)ml·kg-1·min-1],peak oxygen uptake(Peak VO2)[(17.87±0.72)ml·kg-1·min-1 vs.(16.66±0.24)ml·kg-1·min-1],left ventricular ejection fraction(LVEF)[(51.15±2.42)％vs.(44.09±1.94)％],scores of Morisky Medication Adherence Scale(MMAS-8)[(5.29±0.30)points vs.(4.11±0.27)points]and Seattle Angina Questionnaire(SAQ)[(85.50±4.37)points vs.(73.27±2.53)points],and significant lower left ventricular end-diastolic diameter(LVEDd)[(40.51±0.41)mm vs.(46.64±0.99)mm],score of Patient Health Questionnaire-9(PHQ-9)[(7.67±0.85)points vs.(9.66±1.43)points]and total incidence of adverse cardiovascular events within 1-year follow-up(4.00％vs.16.00％)(P＜0.05 or＜0.01).Conclusion:Internet continuous rehabilitation intervention could improve car-diopulmonary exercise capacity and cardiac function,help to improve their quality of life and relieve depression,and reduce the risk of adverse cardiovascular events in CHD patients after PCI.

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

Objective:To investigate mental health literacy and advance care planning(ACP)condition,their influencing fac-tors,and their correlation in elderly patients with coronary heart disease(CHD).Methods:General data of 500 elderly CHD patients admitted in the Second Affiliated Hospital of Chinese PLA Air Force Military Medical University between January 2020 and December 2021 were collected.Mental health literacy and ACP condition were assessed.Multivariate linear regres-sion was used to analyze their influencing factors,and Pearson method was used to analyze their association.Results:Total score of Multicomponent Mental Health Literacy(MHL)was(10.78±2.57)points,and total score of Advance Care Plan-ning Readiness Scale(ACPRS)was(71.41±4.84)points in the 500 elderly CHD patients.Multivariate linear regression a-nalysis indicated that level of disease uncertainty had negative impact on MHL score,presence of spouse and trust in medical care had positive impact on MHL score(P＜0.05 or＜0.01);number of complications had negative impact on ACPR score,while presence of spouse and family mean monthly income had positive impact on ACPRS score(P＜0.05 or＜0.01).Pearson correlation analysis indicated that MHL score was positively correlated with ACPRS score(r=0.476,P＜0.001).Conclusion:Both mental health literacy and ACP status need to be improved in elderly CHD patients.They are posi-tively correlated with each other.Presence of spouse,number of complications and trust in medical care are the important influencing factors.Therefore,medical staff can take targeted measures to improve ACP readiness and mental health quality.

Objective:This study aims to explore the rehabilitation effect of continuous rehabilitation management based on Internet thinking on patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:This randomized controlled study enrolled 100 CHD patients admitted in Second Affiliated Hospi-tal of Chinese PLA Air Force Military Medical University between October 2020 and December 2021.They were di-vided into control group(n=50)and intervention group(n=50).Patients in control group received routine reha-bilitation nursing mode,compared to those in intervention group applying"Internet+"continuous rehabilitation nursing intervention program,both groups were intervened for 3 months.Cardiac function,cardiopulmonary exer-cise test indexes,depression,medication compliance,quality of life and incidence of adverse cardiovascular events within 1-year follow-up were compared between two groups.Results:Compared with patients in control group after 3 months,those in intervention group had significant higher oxygen uptake at anaerobic threshold(VO2@AT)[(11.75±0.39)ml·kg-1·min-1 vs.(10.17±0.76)ml·kg-1·min-1],peak oxygen uptake(Peak VO2)[(17.87±0.72)ml·kg-1·min-1 vs.(16.66±0.24)ml·kg-1·min-1],left ventricular ejection fraction(LVEF)[(51.15±2.42)％vs.(44.09±1.94)％],scores of Morisky Medication Adherence Scale(MMAS-8)[(5.29±0.30)points vs.(4.11±0.27)points]and Seattle Angina Questionnaire(SAQ)[(85.50±4.37)points vs.(73.27±2.53)points],and significant lower left ventricular end-diastolic diameter(LVEDd)[(40.51±0.41)mm vs.(46.64±0.99)mm],score of Patient Health Questionnaire-9(PHQ-9)[(7.67±0.85)points vs.(9.66±1.43)points]and total incidence of adverse cardiovascular events within 1-year follow-up(4.00％vs.16.00％)(P＜0.05 or＜0.01).Conclusion:Internet continuous rehabilitation intervention could improve car-diopulmonary exercise capacity and cardiac function,help to improve their quality of life and relieve depression,and reduce the risk of adverse cardiovascular events in CHD patients after PCI.

Objective To construct a lentiviral vector for overexpression of bone morphogenetic protein 7(BMP7)in mice,and the effect of BMP7 overexpression on the expression of Jagged1 in mouse aortic endothelial cells and the calcification of the co-cultured vascular smooth muscle cells(VSMCs)were analyzed.Methods According to the target gene information Mouse-BMP7(NM_007557.3)and plasmid information pLVX-zsGreen-C1,gene sequence synthesis was carried out to construct BMP7 overexpression lentivirus.The efficiency of BMP7 overexpression lentivirus infection was detected by qPCR;the expression of Jagged1 protein in aortic endothelial cells from infected mice was detected by Western blot.The endothelial cells with lentivirus overexpressing BMP7 were co-cultured with VSMCs,and the calcification of VSMCs was observed by alizarin red staining.Results BMP7 overexpression lentiviral vector was successfully constructed and transfected into aortic endothelial cells.qPCR test results showed that the expression level of BMP7 mRNA was significantly increased in the BMP7 overexpression group than that in the normal control group(P<0.01),while there was no significant difference in the expression of BMP7 mRNA between the empty vector control group and the normal control group(P>0.05).Western blot results showed that the expression level of Jagged1 protein in endothelial cells of mouse in the BMP7 overexpression group was significantly lower than that in the normal control group(P<0.01),while there was no significant difference in the expression level of Jagged1 protein in endothelial cells between the empty vector control group and the normal control group(P>0.05).The results of alizarin red staining showed that the calcification of VSMCs was significantly increased after co-cultured with endothelial cells infected with BMP7 lentivirus.Conclusion Mouse BMP7 overexpression lentiviral vector was successfully constructed,and overexpression of BMP7 can reduce the expression of Jagged1 in mouse aortic endothelial cells and promote the calcification of co-cultured VSMCs.

The anti-inflammatory effect of simplified Zhiqin Decoction was observed by using lipopolysaccharide (LPS)-induced inflammation mouse model. The main chemical constituents and the main mechanism of action of simplified Zhiqin Decoction were predicted by network pharmacology. Animal experiments verified the anti-inflammatory mechanism of simplified Zhiqin Decoction (this experiment was approved by the Animal Experiment Ethics Committee of Southwest University, approval number: IACUC-20210825-02). Simplifying Zhiqin Decoction has a significant anti-inflammatory effect on inflammatory mice, can significantly improve the overall macro shape of mice, reduce body temperature, water intake, increase the number of autonomous activities; alleviate liver, lung, spleen, thymus inflammation and pathological damage; decrease tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, nitric oxide (NO), prostaglandin E₂ (PGE₂) content in serum and urine. The contents of serum immune factors IgG, IgA and IgM were increased. Network pharmacology predicted 66 potential anti-inflammatory active components of simplified Zhiqin Decoction involving 132 inflammatory targets, and the key anti-inflammatory signaling pathway involved PI3K/AKT, TNF, JAK-STAT, etc. Animal experiments show that simplified Zhiqin Decoction can significantly reduce the expression of JAK2/STAT-PI3K/AKT-NF-κB-TNF signaling pathway related proteins in lung tissue of inflammatory mice. The results of this study showed that simplified Zhiqin Decoction had significant anti-inflammatory effects, and its main anti-inflammatory components were quercetin, β-sitosterol, kaempferol, wogonin, stigmasterol, luteolin, neobaicalein, etc. The main mechanism of its anti-inflammatory action is that it significantly inhibits the expression of JAK2/STAT-PI3K/AKT-NF-κB-TNF signaling pathway protein.