Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective To screen antidepressant-active compounds from Polygonati Rhizoma and explore their effects and possible mechanisms against depression induced by simulated weightlessness.Methods A systems pharmacology approach was used to screen potential antidepressant-active compounds and their targets from Polygonati Rhizoma.The hindlimb unloading(HLU)rat model was employed for the study.Twenty-four healthy male Sprague-Dawley rats were randomly divided into three groups:control group(administered 0.5%carboxymethylcellulose by gavage),HLU group(hindlimb unloading),and HLU+treatment group(hindlimb unloading+active compound gavage),with 8 rats in each group.After 28 days of hindlimb unloading,depressive-like behaviors in rats were evaluated using the forced swimming test and tail suspension test.Hippocampal morphology was examined with H&E staining,and GO and KEGG enrichment analyses were conducted on the targets of active compounds.Results A total of 38 active compounds were screened from Polygonati Rhizoma,among which apigenin had an oral bioavailability of 23.06%and a drug-likeness score of 0.21.Compound-target network analysis indicated that apigenin had the highest degree and betweenness centrality values,suggesting it might be the key active component with antidepressant potential in Polygonati Rhizoma.In the forced swimming and tail suspension tests,rats in the HLU group showed a significant increase in immobility time compared to the control group,indicating successful establishment of the depression model.However,compared to the HLU group,rats in the HLU plus apigenin group exhibited significantly reduced immobility time.The H&E staining results of hippocampal tissue showed a significant reduction in the number of hippocampal neurons,along with numerous shrunken neurons and small vacuoles in nerve fibers in the HLU group.In contrast,the treatment group exhibited an increased number of hippocampal neurons,with improved cellular morphology.Target enrichment analysis indicated that apigenin targets were mainly involved in the regulation of apoptosis and cancer-related signaling pathways.Conclusion Apigenin significantly improved depressive-like behaviors in rats subjected to hindlimb unloading,and it has a protective effect on hippocampal tissue.It may provide a new natural active compound for the treatment of depression caused by spaceflight-induced weightlessness.

Objective To analyze the impact of sarcopenia on the efficacy and adverse reactions of immunotherapy combined with chemotherapy in patients with advanced gastric cancer.Methods Patients with locally advanced or metastatic gastric cancer confirmed by pathology who were not eligible for radical surgery were selected as study subjects.A body composition analyzer was used to measure the appendicular muscle mass of the patients and calculate the skeletal muscle mass index(SMI).Based on the SMI,the patients were divided into sarcopenia group and non-sarcopenia group.On the basis of nutritional intervention and comprehensive exercise therapy,the patients were administered immu-notherapy combined with chemotherapy.The efficacy and adverse reactions were evaluated.The primary endpoint was progression-free survival(PFS),and the secondary endpoints were the objec-tive response rate(ORR)and treatment-related adverse reactions.Results A total of 52 gastric cancer patients were included,with 23 in the sarcopenia group and 29 in the non-sarcopenia group.The median PFS in the non-sarcopenia group was 9.8 months(95％CI,8.9 to 12.4),and was 5.4 months in the sarcopenia group(95％CI,4.9 to 8.1).The median PFS in the non-sarcopenia group was longer than that in the sarcopenia group,and the difference was statistically significant[HR(95％CI)=0.41(0.23 to 0.73),P=0.003].The results of the multivariate Cox propor-tional hazards regression model showed that comorbidities,treatment cycles,and sarcopenia were all independent prognostic factors affecting the PFS of gastric cancer patients(P＜0.05).The ORR in the non-sarcopenia group was 48.28％(14/29),and was 17.39％(4/23)in the sarcopenia group(x2=5.276,P＜0.05).Treatment-related adverse reactions with grading ≥3 in both groups were mainly hematological toxicities.In the non-sarcopenia group,the incidence of grading ≥ 3 treat-ment-related adverse reactions was 27.59％(8/29),and the incidence of grading＜3 treatment-re-lated adverse reactions(including those with no adverse reactions)was 72.41％(21/29).In the sarcopenia group,the incidence of grading ≥3 treatment-related adverse reactions was 56.52％(13/23),and the incidence of grading＜3 treatment-related adverse reactions(including those without adverse reactions)was 43.48％(10/23).The incidence of grading ≥3 treatment-related adverse reactions in the non-sarcopenia group was lower than that in the sarcopenia group(P=0.035).Conclusion For patients with locally advanced or metastatic gastric cancer complicated with sarcopenia,the median PFS of immunotherapy combined with chemotherapy is shorter,the ORR is lower,and the incidence of treatment-related adverse reactions is increased.Therefore,ear-ly intervention for sarcopenia should be implemented to improve the quality of life of patients with advanced gastric cancer.

Objective To determine the effect of baicalein on high glucose-induced cardiac fibro-blast pyroptosis based on the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)pathway.Methods Rat cardiac fibroblasts were grouped into control,high glucose group,low-,medium-and high-dose baicalein(H-,M-and L-baicalein)groups,and H-baicalein+NLRP3 agonist(BMS-986299)group.Except for the control group,all other groups were cultured in DMEM medium containing 40 mmol/L glucose,then 12.5,25 and 50 μmol/L baicalein was added into the medium correspondingly,and 1 μmol/L BMS-986299 was used to treat the H-baicalein+NLRP3 agonist group.Lactate dehydrogenase(LDH)cytotoxicity assay were employed to detect cell cytotoxicity.qRT-PCR and Western blotting were performed to determine the expression of NLRP3,Caspase-1,and GSDMD at mRNA and protein levels.Results High glucose treatment induced more EdU positive cells,higher pyroptotic rate,stronger cytotoxicity,higher Col-Ⅰ and Col-Ⅲ contents,and enhanced mRNA and protein levels of NLRP3,Caspase-1 and GSDMD in comparison to the control group(P＜0.05).The H-baicalein+NLRP3 agonist group had more EdU positive cells(26.85±2.95 cells vs 15.43±1.82 cells,P＜0.05),higher pyroptotic rate[(33.45±4.02)％vs(17.34±2.15)％,P＜0.05],stronger cytotoxicity[(27.94±2.93)％vs(14.13±1.87)％,P＜0.05],and increased contents of Col-Ⅰ(107.58±13.39 ng/ml vs 58.73±8.36 ng/ml,P＜0.05)and Col-Ⅲ(118.43±13.95 ng/ml vs 68.74±8.57 ng/ml,P＜0.05),and enhanced expression of NLRP3,Caspase-1 and GSDMD at both mRNA and protein levels(P＜0.05)when compared with the H-baicalein group.Conclusion Baicalein inhibits high glucose-induced cardiac fibroblast pyroptosis by suppressing NLRP3/Caspase-1/GSDMD pathway.

Objective:To investigate the effect of taxifolin on cartilage damage in osteoarthritis(OA)rats by regulating Sonic hedgehog(Shh)/Gli family zinc finger protein 1(Gli1)signaling pathway.Methods:Rats were randomly separated into control group,OA group,taxifolin group,Shh activator(purmorphamine)group and taxifolin+purmorphamine group,with 12 rats in each group.Except for control group,rats in all other groups were used to construct OA models by the improved Hulth method.After successful modeling,medication treatment began once a day for 4 weeks.Changes in knee joint swelling and maximum range of motion in rats were detected.Saffranine O-solid green staining was applied to detect pathological changes in knee joint cartilage tissue and to perform the Osteoarthritis Research Society International(OARSI)score.ELISA was applied to detect levels of IL-1β,TNF-α and IL-10 in tissue.Immunohistochemical staining was applied to detect expressions of ADAMTS-5 and MMP-13 in knee joint cartilage tissue.Western blot was applied to detect expressions of Shh and Gli1 proteins in knee joint cartilage tissue.Results:Compared with control group,cartilage surface of rats in OA group was damaged,cartilage erosion occurred,and cells were greatly reduced,knee joint swelling,OARSI score,levels of IL-1β and TNF-α in knee cartilage tissue,percentages of ADAMTS-5 and MMP-13 positive cells,Shh and Gli1 protein expressions were elevated,the maximum range of motion and level of IL-10 in knee cartilage tissue were decreased(P<0.05).Compared with OA group,damage to cartilage surface,cartilage erosion and cell reduction were alleviated in taxifolin group,knee joint swelling,OARSI score,levels of IL-1β and TNF-α in knee cartilage tissue,percentages of ADAMTS-5 and MMP-13 positive cells,Shh and Gli1 protein expressions were decreased,while the maximum range of motion and level of IL-10 in knee cartilage tissue were increased,the trend of changes in corresponding indicators in purmorphamine group was opposite to that in taxifolin group(P<0.05).Compared with taxifolin group,pathological damage to knee joint cartilage tissue in taxifolin+purmorphamine group was intensified,knee joint swelling,OARSI score,levels of IL-1β and TNF-α in knee cartilage tissue,percentages of ADAMTS-5 and MMP-13 positive cells,Shh and Gli1 protein expressions were increased,the maximum range of motion and level of IL-10 in knee carti-lage tissue were decreased(P<0.05).Conclusion:The improvement mechanism of taxifolin on cartilage damage in OA rats may be related to the inhibition of the Shh/Gli1 signaling pathway.

Objective:To investigate the serum level of soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with multiple myeloma (MM) and its effect on the therapeutic effect of daletumab.Methods:A total of 126 MM patients admitted to the Affiliated Hospital of Jining Medical College from June 2019 to June 2021 were retrospectively selected as the observation group, and 120 healthy subjects in the same period were selected as the control group. The observation group was treated with daletumab. The level of sVCAM-1 in the observation group and the control group was compared, and the relationship between serum sVCAM-1 level and clinicopathological features, different Durie-Salmon (DS) stages, different International Staging System(ISS) stages and treatment outcome of MM patients were analyzed.Results:The serum level of sVCAM-1 in the observation group was higher than that in the control group: (797.69 ± 119.73) μg/L vs. (210.55 ± 73.77) μg/L, there was statistical difference ( P<0.01). There were no statistical differences in serum sVCAM-1 level among MM patients with different sex, body mass index, blood calcium, serum albumin, hemoglobin, lactate dehydrogenase and diagnostic type ( P>0.05). The serum level of sVCAM-1 in MM patients DS stage Ⅰ, Ⅱ and Ⅲ were (649.29 ± 101.02), (694.36 ± 109.88) and (729.66 ± 120.44) μg/L, there was statistical difference ( F = 5.12, P<0.01). The serum level of sVCAM-1 in MM patients with ISS stage Ⅰ, Ⅱ and Ⅲ were (648.73 ± 99.77), (701.05 ± 107.83) and (765.82 ± 111.07) μg/L, there was statistical difference ( F = 11.46, P<0.01). After treatment, the serum level of sVCAM-1 in MM patients with complete remission, partial remission and relapse were (234.05 ± 90.73), (445.36 ± 97.11) and (793.05 ± 121.03) μg/L, there was statistical difference ( F = 245.15, P<0.01). The results of receiver operating characteristic (ROC) curve analysis showed that when the cut-off value of serum sVCAM-1 level was 58.50 μg/L, the area under the curve (AUC) was 0.762 (95% CI 0.699 - 0.825, P<0.01), the sensitivity was 80.95%, the specificity was 67.50%, and the accuracy was 74.39%. Conclusions:The level of serum sVCAM-1 in MM patients is significantly increased, and the higher the level of SVCAM-1, the worse the prognosis of patients, which can be used as one of the indicator to predict the therapeutic effect of MM patients.

Objective:To investigate the effect of taxifolin on cartilage damage in osteoarthritis(OA)rats by regulating Sonic hedgehog(Shh)/Gli family zinc finger protein 1(Gli1)signaling pathway.Methods:Rats were randomly separated into control group,OA group,taxifolin group,Shh activator(purmorphamine)group and taxifolin+purmorphamine group,with 12 rats in each group.Except for control group,rats in all other groups were used to construct OA models by the improved Hulth method.After successful modeling,medication treatment began once a day for 4 weeks.Changes in knee joint swelling and maximum range of motion in rats were detected.Saffranine O-solid green staining was applied to detect pathological changes in knee joint cartilage tissue and to perform the Osteoarthritis Research Society International(OARSI)score.ELISA was applied to detect levels of IL-1β,TNF-α and IL-10 in tissue.Immunohistochemical staining was applied to detect expressions of ADAMTS-5 and MMP-13 in knee joint cartilage tissue.Western blot was applied to detect expressions of Shh and Gli1 proteins in knee joint cartilage tissue.Results:Compared with control group,cartilage surface of rats in OA group was damaged,cartilage erosion occurred,and cells were greatly reduced,knee joint swelling,OARSI score,levels of IL-1β and TNF-α in knee cartilage tissue,percentages of ADAMTS-5 and MMP-13 positive cells,Shh and Gli1 protein expressions were elevated,the maximum range of motion and level of IL-10 in knee cartilage tissue were decreased(P<0.05).Compared with OA group,damage to cartilage surface,cartilage erosion and cell reduction were alleviated in taxifolin group,knee joint swelling,OARSI score,levels of IL-1β and TNF-α in knee cartilage tissue,percentages of ADAMTS-5 and MMP-13 positive cells,Shh and Gli1 protein expressions were decreased,while the maximum range of motion and level of IL-10 in knee cartilage tissue were increased,the trend of changes in corresponding indicators in purmorphamine group was opposite to that in taxifolin group(P<0.05).Compared with taxifolin group,pathological damage to knee joint cartilage tissue in taxifolin+purmorphamine group was intensified,knee joint swelling,OARSI score,levels of IL-1β and TNF-α in knee cartilage tissue,percentages of ADAMTS-5 and MMP-13 positive cells,Shh and Gli1 protein expressions were increased,the maximum range of motion and level of IL-10 in knee carti-lage tissue were decreased(P<0.05).Conclusion:The improvement mechanism of taxifolin on cartilage damage in OA rats may be related to the inhibition of the Shh/Gli1 signaling pathway.

Objective:To investigate the serum level of soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with multiple myeloma (MM) and its effect on the therapeutic effect of daletumab.Methods:A total of 126 MM patients admitted to the Affiliated Hospital of Jining Medical College from June 2019 to June 2021 were retrospectively selected as the observation group, and 120 healthy subjects in the same period were selected as the control group. The observation group was treated with daletumab. The level of sVCAM-1 in the observation group and the control group was compared, and the relationship between serum sVCAM-1 level and clinicopathological features, different Durie-Salmon (DS) stages, different International Staging System(ISS) stages and treatment outcome of MM patients were analyzed.Results:The serum level of sVCAM-1 in the observation group was higher than that in the control group: (797.69 ± 119.73) μg/L vs. (210.55 ± 73.77) μg/L, there was statistical difference ( P<0.01). There were no statistical differences in serum sVCAM-1 level among MM patients with different sex, body mass index, blood calcium, serum albumin, hemoglobin, lactate dehydrogenase and diagnostic type ( P>0.05). The serum level of sVCAM-1 in MM patients DS stage Ⅰ, Ⅱ and Ⅲ were (649.29 ± 101.02), (694.36 ± 109.88) and (729.66 ± 120.44) μg/L, there was statistical difference ( F = 5.12, P<0.01). The serum level of sVCAM-1 in MM patients with ISS stage Ⅰ, Ⅱ and Ⅲ were (648.73 ± 99.77), (701.05 ± 107.83) and (765.82 ± 111.07) μg/L, there was statistical difference ( F = 11.46, P<0.01). After treatment, the serum level of sVCAM-1 in MM patients with complete remission, partial remission and relapse were (234.05 ± 90.73), (445.36 ± 97.11) and (793.05 ± 121.03) μg/L, there was statistical difference ( F = 245.15, P<0.01). The results of receiver operating characteristic (ROC) curve analysis showed that when the cut-off value of serum sVCAM-1 level was 58.50 μg/L, the area under the curve (AUC) was 0.762 (95% CI 0.699 - 0.825, P<0.01), the sensitivity was 80.95%, the specificity was 67.50%, and the accuracy was 74.39%. Conclusions:The level of serum sVCAM-1 in MM patients is significantly increased, and the higher the level of SVCAM-1, the worse the prognosis of patients, which can be used as one of the indicator to predict the therapeutic effect of MM patients.

Objective To determine the effect of baicalein on high glucose-induced cardiac fibro-blast pyroptosis based on the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)pathway.Methods Rat cardiac fibroblasts were grouped into control,high glucose group,low-,medium-and high-dose baicalein(H-,M-and L-baicalein)groups,and H-baicalein+NLRP3 agonist(BMS-986299)group.Except for the control group,all other groups were cultured in DMEM medium containing 40 mmol/L glucose,then 12.5,25 and 50 μmol/L baicalein was added into the medium correspondingly,and 1 μmol/L BMS-986299 was used to treat the H-baicalein+NLRP3 agonist group.Lactate dehydrogenase(LDH)cytotoxicity assay were employed to detect cell cytotoxicity.qRT-PCR and Western blotting were performed to determine the expression of NLRP3,Caspase-1,and GSDMD at mRNA and protein levels.Results High glucose treatment induced more EdU positive cells,higher pyroptotic rate,stronger cytotoxicity,higher Col-Ⅰ and Col-Ⅲ contents,and enhanced mRNA and protein levels of NLRP3,Caspase-1 and GSDMD in comparison to the control group(P＜0.05).The H-baicalein+NLRP3 agonist group had more EdU positive cells(26.85±2.95 cells vs 15.43±1.82 cells,P＜0.05),higher pyroptotic rate[(33.45±4.02)％vs(17.34±2.15)％,P＜0.05],stronger cytotoxicity[(27.94±2.93)％vs(14.13±1.87)％,P＜0.05],and increased contents of Col-Ⅰ(107.58±13.39 ng/ml vs 58.73±8.36 ng/ml,P＜0.05)and Col-Ⅲ(118.43±13.95 ng/ml vs 68.74±8.57 ng/ml,P＜0.05),and enhanced expression of NLRP3,Caspase-1 and GSDMD at both mRNA and protein levels(P＜0.05)when compared with the H-baicalein group.Conclusion Baicalein inhibits high glucose-induced cardiac fibroblast pyroptosis by suppressing NLRP3/Caspase-1/GSDMD pathway.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.