Objective To explore the therapeutic effect of corosolic acid on melanoma and its possible molecular mechanisms.Methods Melanoma B16 cells and A375 cells were cultured and divided into control group(0μmol/L),low concentration corosolic acid group(5μmol/L),medium concentration corosolic acid group(10μmol/L),and high concentration corosolic acid group(20μmol/L).According to the grouping,the two types of cells were intervened with corresponding concentrations of corosolic acid.Then,the cell prolif-eration activity was detected by colony formation assay,the cell migration ability was detected by scratch assay,and the cell invasion abili-ty was detected by Transwell assay.Western blot analysis was performed to detect the expression levels of transforming growth factor-β1(TGF-β1),mothers against DPP hom 2(Drosophila)(SMAD2),SMAD3,phosphorylated SMAD2(p-SMAD2),phosphorylated SM3(p-SMAD3),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),and Bcl-2 associated death promoter(Bad)in cells.Immunofluorescence staining was used to detect the expression levels of N-cadherin and Vimentin in cells.For response experi-ments,TGF-β1 recombinant protein was added to the cell culture system of the corosamic acid treated groups as described above.Results Compared with the blank group cells,intervention with different concentrations of corosolic acid significantly inhibited the prolif-eration,migration,and invasion activities of B16 cells and A375 cells,showing a concentration-dependent effect.Additionally,corosol-ic acid intervention led to a significant decrease in the expression levels of TGF-β1,p-SMAD2,p-SMAD3,Bcl-2,N-cadherin,and Vimentin proteins within melanoma cells,while significantly increasing the expression levels of Bax and Bad proteins.However,there was no significant change in the expression levels of SMAD2 and SMAD3 proteins.After adding recombinant TGF-β1 protein,the inhibi-tory effect of corosolic acid on melanoma cells was partially reversed.Conclusion Corosolic acid can significantly inhibit the prolifera-tion,migration,and invasion activities of melanoma cells,and this is related to its inhibition of the TGF-β1/SMAD2/3 pathway.

Objective To address the issue of noise in medical images,this paper proposes a left ventricular image segmentation method integrated with a denoising module to improve segmentation accuracy.Methods The denoising module is based on a denoising diffusion probabilistic model,and the segmentation model includes two branches:motion estimation and segmentation.This paper modifies the prediction target of the denoising module to the original signal instead of noise,enabling the end-to-end cascade training process of the denoising module and the segmentation model.Results On the EchoNet-Dynamic dataset,the segmentation performance of traditional denoising methods was inferior to the benchmark model;the Noise2Noise model showed improvement in three metrics,while our proposed method achieved improvement in all four metrics.On the ACDC dataset,our method outperformed the benchmark model,while other methods either performed worse than the benchmark or showed no statistical difference.Conclusion Traditional denoising methods can impair segmentation performance,whereas our proposed method can stably and effectively improve segmentation performance.Experiments verify the feasibility and potential clinical application value of the proposed method.

Objective To address the issue of noise in medical images,this paper proposes a left ventricular image segmentation method integrated with a denoising module to improve segmentation accuracy.Methods The denoising module is based on a denoising diffusion probabilistic model,and the segmentation model includes two branches:motion estimation and segmentation.This paper modifies the prediction target of the denoising module to the original signal instead of noise,enabling the end-to-end cascade training process of the denoising module and the segmentation model.Results On the EchoNet-Dynamic dataset,the segmentation performance of traditional denoising methods was inferior to the benchmark model;the Noise2Noise model showed improvement in three metrics,while our proposed method achieved improvement in all four metrics.On the ACDC dataset,our method outperformed the benchmark model,while other methods either performed worse than the benchmark or showed no statistical difference.Conclusion Traditional denoising methods can impair segmentation performance,whereas our proposed method can stably and effectively improve segmentation performance.Experiments verify the feasibility and potential clinical application value of the proposed method.

Objective To explore the therapeutic effect of corosolic acid on melanoma and its possible molecular mechanisms.Methods Melanoma B16 cells and A375 cells were cultured and divided into control group(0μmol/L),low concentration corosolic acid group(5μmol/L),medium concentration corosolic acid group(10μmol/L),and high concentration corosolic acid group(20μmol/L).According to the grouping,the two types of cells were intervened with corresponding concentrations of corosolic acid.Then,the cell prolif-eration activity was detected by colony formation assay,the cell migration ability was detected by scratch assay,and the cell invasion abili-ty was detected by Transwell assay.Western blot analysis was performed to detect the expression levels of transforming growth factor-β1(TGF-β1),mothers against DPP hom 2(Drosophila)(SMAD2),SMAD3,phosphorylated SMAD2(p-SMAD2),phosphorylated SM3(p-SMAD3),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),and Bcl-2 associated death promoter(Bad)in cells.Immunofluorescence staining was used to detect the expression levels of N-cadherin and Vimentin in cells.For response experi-ments,TGF-β1 recombinant protein was added to the cell culture system of the corosamic acid treated groups as described above.Results Compared with the blank group cells,intervention with different concentrations of corosolic acid significantly inhibited the prolif-eration,migration,and invasion activities of B16 cells and A375 cells,showing a concentration-dependent effect.Additionally,corosol-ic acid intervention led to a significant decrease in the expression levels of TGF-β1,p-SMAD2,p-SMAD3,Bcl-2,N-cadherin,and Vimentin proteins within melanoma cells,while significantly increasing the expression levels of Bax and Bad proteins.However,there was no significant change in the expression levels of SMAD2 and SMAD3 proteins.After adding recombinant TGF-β1 protein,the inhibi-tory effect of corosolic acid on melanoma cells was partially reversed.Conclusion Corosolic acid can significantly inhibit the prolifera-tion,migration,and invasion activities of melanoma cells,and this is related to its inhibition of the TGF-β1/SMAD2/3 pathway.

Objective To systematically evaluate the rumination in stroke patients and identify the influencing factors.Methods A mixed-methods systematic review was carried out by searching databases,such as CNKI,WanFang Data,VIP,CBM,PubMed,Web of Science,the Cochrane Library,Embase and Scopus databases,from the inception to 27th October,2023,for literature on the influencing factors of rumination in stroke patients.The researchers evaluated quality of the literature according to the mixed methods appraisal tool developed by McGill University of Canada.Then the data were collected,analysed and integrated using the convergent integration method proposed by the JBI Evidence-Based Health Care Research Centre of Australia.Results A total of 22 studies were included with an involvement of 4 949 patients.Then a total of 45 research topics were extracted and grouped into 8 categories.The influence factors of rumination were integrated,including individual factors,external support and coping strategies.Conclusions Stroke patients have different levels of rumination.Individual factors may affect rumination in patients.Harmonious interpersonal relationships and positive thinking with coping strategies can promote deliberate rumination.However,the effects of age,place of residence and household income on rumination in stroke patients are required to be further explored.

Objective To investigate the association between plasma Klotho protein level and lacunar cerebral infarction in the elderly.Methods Eighty eight patients with lacunar cerebral infarction aged over 60 years were selected as the observation group,and 90 age-and gender-matched elderly patients without lacunar infarction as the control group.The protein level of Klotho was tested by enzyme linked immunosorbent assay (ELISA).Klotho protein level was compared between the observation and control groups.The correlation between plasma Klotho level and lacunar infarction in elderly patients was analyzed.Results Compared with the control group,lacunar infarction group showed that Klotho protein level was decreased [(689.4±40.8) ng/L vs.(848.5±38.7) ng/L,P=0.009],and the proportion of patients with hypertension was increased (83.0％ vs.66.7％,P=0.04).There was no significant difference in age,gender,body mass index (BMI),dyslipidemia,diabetes mellitus and coronary heart disease between the two groups.The multivariate logistic regression analysis showed that the low plasma level of Klotho protein and hypertension were identified as the independent risk factors for Lacunar infarction (OR=3.325 and 2.413,P=0.003 and 0.021,respectively).Conclusions Klotho protein level may be associated with lacunar cerebral infarction in elderly people.Monitoring plasma Klotho protein level has an important clinical significance in the prevention,diagnosis and prognosis of lacunar cerebral infarction.

Objective To explore the correlation between plasma Klotho and FGF23 levels with senile hypertension .Methods Totally 180 cases of hypertension aged more than 60 years old were selected as the research group and divided into the grade 1 hypertension group(60 cases) ,grade 2 hypertension group(60 cases) and grade 3 hypertension group(60 cases) .The age and pro‐portion of male to female were basically consistent .60 elderly people without hypertension were selected as the control group .The level of plasma Klotho and FGF23 protein were tested by ELISA .The lipid level was detected by the automatic biochemical analy‐zer .The detection results were compared with those in the control group for analyzing their correlation .Results Plasma Klotho protein level in each hypertension group was lower than that in the control group ,while plasma FGF23 protein level and BMI were significantly higher than those in the control group(P<0 .05) .With the blood pressure level increase ,plasma Klotho protein level was gradually decreased ,while FGF23 protein level was gradually increased .The negative correlation was found between plasma Klotho protein and FGF23 protein (r= -0 .282 ,P=0 .001) .Plasma Klotho protein and FGF23 protein had no obvious correlation with BMI (r= -0 .063 ,-0 .098 ,P>0 .05) .Conclusion Plasma Klotho protein and FGF23 protein levels have obvious correlation with the blood pressure level ,which may jointly participate in the occurrence and development of hypertension .