1.Efficacy and Safety of Blinatumomab in Adult Patients with B-Cell Acute Lymphoblastic Leukemia
Ya-Lei HU ; Yong-Feng SU ; Yang LI ; Xuan ZHENG ; An WANG ; Yi-Zhi WANG ; Lei XU ; Chun-Ji GAO ; Liang-Ding HU ; Dai-Hong LIU ; Xiao-Ning GAO
Journal of Experimental Hematology 2025;33(6):1571-1576
Objective:To evaluate the efficacy and safety of blinatumomab in adult patients with relapsed/refractory(R/R)or measurable residual disease(MRD)positive B-cell acute lymphoblastic leukemia(B-ALL)in the real world.Methods:The clinical data of 30 B-ALL patients received at least 1 course of blinatumomab therapy in the Chinese PLA General Hospital from January 1st,2021 to December 31st,2023 were retrospectively analyzed,including pre-treatment baseline clinical feature,post-treatment complete response(CR),CR with partial hematologic recovery(CRh),CR with incomplete hematologic recovery(CRi),complete MRD response rate,MRD response rate(MRD<10-4),overall survival(OS),and disease-free survival(DFS),as well as drug-related adverse reactions.Results:Among 5 patients who were not assessed 4 were MRD negative and 1 did not receive bone marrow biopsy.In the R/R B-ALL group(13 cases),11 patients achieved CR/CRh/CRi and 10 patients achieved complete MRD response.In MRD+group(12 cases),9 patients achieved overall MRD response and 7 patients achieved complete MRD response.The median follow-up time was 8.4(95%CI:6.3-10.4)months.The median OS was 15.5(95%CI:0.7-30.3)months in the R/R group,while not reached in the MRD+group.The median DFS of the two groups were not reached.Drug-related adverse reactions occurred in 22 patients,and pyrexia was the most common(13 cases).Grade ≥3 adverse reactions occurred in 15 patients,and neutropenia was the most common(9 cases).Cytokine release syndrome occurred in 6 patients,including 5 cases with grade 1 and 1 case with grade 3.No patients interrupted therapy or died due to drug-related adverse reactions.Conclusion:Blinatumomab is effective in the treatment of R/R or continuous MRD+B-ALL with acceptable adverse reactions.
2.Correlation between D-dimer, antithrombin Ⅲ levels and multiple organ dysfunction syndrome in patients with severe multiple trauma
Kang TOU ; Laifa KONG ; Zhi WANG ; Yong′an XU
Chinese Journal of Postgraduates of Medicine 2025;48(7):577-584
Objective:To explore the correlation between D-dimer (D-D), antithrombin Ⅲ (AT-Ⅲ) at admission, and multiple organ dysfunction syndrome (MODS) in patients with severe multiple trauma.Methods:A retrospective study was conducted to collect data from 80 patients with severe multiple trauma admitted to Jinhua Central Hospital from April 2021 to April 2024. According to the occurrence of MODS within 1 week of treatment, the patients were divided into an occurrence group with 25 cases and a non-occurrence group with 55 cases. The general data, plasma D-D, serum AT-Ⅲ levels and other laboratory indexes at admission were compared between the two groups. The correlation between D-D, AT-Ⅲ at admission and MODS in patients with severe multiple trauma was analyzed.Results:The injury severity rating score (ISS) in the occurrence group was higher than that in the non-occurrence group: (29.12 ± 3.84) points vs. (26.18 ± 3.12) points, the proportion of damage control surgery was lower than that in the non-occurrence group: 32.00% (8/25) vs. 65.45% (36/55), the platelet, AT-Ⅲ and albumin at admission were lower than those in the non-occurrence group: (112.28 ± 20.12) ×10 9/L vs. (123.56 ± 23.47) ×10 9/L, (133.79 ± 18.21) mg/L vs. (148.26 ± 19.57) mg/L, (35.12 ± 6.35) g/L vs. (38.47 ± 5.88) g/L, the D-D at admission was higher than that in the non-occurrence group: (11.36 ± 3.35) mg/L vs. (8.18 ± 2.83) mg/L, and there were statistical differences ( P<0.05). Multivariate Logistic regression analysis result showed that the occurrence of MODS in patients with severe multiple trauma may be related to the ISS at admission, the status of receiving damage control surgery, and the D-D, AT-Ⅲ, albumin at admission ( OR = 1.29, 0.14, 1.34, 0.95 and 0.87; P<0.05). Restrictive cubic spline analysis showed that the risk of MODS in patients with severe multiple trauma showed a non-linear dose-response relationship with D-D and AT-Ⅲ at admission ( P<0.05). When D-D at admission ≥ 9.25 mg/L, the risk of MODS increased with increasing levels, while when AT-Ⅲ at admission ≤ 143.49 mg/L, the risk of MODS increased with decreasing levels. The D-D and AT-Ⅲ at admission had a negative interactive effect on the occurrence of MODS in patients with severe multiple trauma. By drawing decision curves and column charts, it was found that D-D and AT-Ⅲ at admission, as well as other major indicators, had high predictive power for the occurrence of MODS in patients with severe multiple trauma. Conclusions:The occurrence of MODS in patients with severe multiple trauma may be related to the levels of D-D and AT-Ⅲ, and the risk of MODS increases with the increase of D-D and the decrease of AT-Ⅲ at admission. Both can effectively assist other indicators in predicting the risk of MODS in patients.
3.Bone marrow mesenchymal stem cell-derived exosomes inhibit dexamethasone-induced C2C12 myotube atrophy
Yi-bing KE ; Yong-hong DING ; Budoukeremu·DA-wuti A ; Hao-ran GUO ; Zhi-jie LAN ; Yong-ping WANG
Chinese Pharmacological Bulletin 2025;41(1):50-56
Aim To investigate the effect of exosomes derived from bone marrod-derived mesenchymal stem cells(BMSCs)on dexamethasone-induced C2C12 muscular canal atrophy.Methods(1)C57BL/6J mouse bone marrow mesenchymal stem cells were isola-ted and cultured by whole bone marrow adhesion meth-od.(2)Extraction and identification of BMSCs EXOs were performed.(3)Myogenic differentiation of C2C12 cells was carried out.(4)The successfully differentia-ted myotubes were divided into the control group(cul-tured in 2%equine serum medium for 48 h),dexam-ethasone group(dexamethasone,DEX,10 μmol·L-1 concentration of DEX interfered with myotubes for 48 h),and exosomes group(exosomes,EXOs,interfered with myotubes for 48 h),exosome inhibitor group(exo-somes extracted from BMSCs after 10 μm GW4869 in-tervention,interfered with myotubes for 48 h).48 h later,the morphology and diameter of muscle tubes were observed and measured by microscope.Cell via-bility of each group was detected by CCK-8 method.The expression levels of atrogin-1 and MuRF-1,myo-genic differentiation antigen(MYOD)in each group were detected by Western blot.Results BMSCs were long spusiform,and BMSCS-EXOS showed a circular bilayer structure under transmission electron microsco-py,with a diameter of about 200 nm.CD9,CD63 and CD81 were highly expressed.Compared with the con-trol group,cell activity in DEX group decreased(P<0.01),diameter of myotubes decreased(P<0.01),expressions of atrogin-1(P<0.05)and MuRF-1(P<0.01)were significantly up-regulated,and expression of MYOD(P<0.01)was significantly down-regula-ted.Compared with the DEX group,cell activity in the BMSCs-EXOs group increased(P<0.01),diameter of myotubes increased(P<0.01),expressions of atrogin-1(P<0.05)and MuRF-1(P<0.01)were signifi-cantly down-regulated,and expression of MYOD(P<0.01)was up-regulated.Compared with the BMSCs-EXOs group,cell activity of the BMSCs-EXOs(GW4869)group decreased(P<0.05),diameter of myotubes decreased(P<0.01),expressions of atrog-in-1(P<0.05)and MuRF-1(P<0.05)were up-regulated,and expression of MYOD(P<0.01)was down-regulated.Conclusion Bone marrow mesen-chymal stem cell-derived exosomes(BM-MSCs-EXOs)inhibit dexamethasone-induced C2C12 muscle tube at-rophy.
4.Application of 4K fluorescence single-port thoracoscopic anatomical segmentectomy in small pulmonary nodules
Zhi-hai WANG ; Miao-miao LIN ; Kun YANG ; Geng GENG ; Yong TAO
Journal of Regional Anatomy and Operative Surgery 2025;34(4):337-341
Objective To analyze the feasibility and advantage of indocyanine green(ICG)fluorescence imaging technique in the thoracoscopic anatomical segmentectomy.Methods Patients with small pulmonary nodules who underwent thoracoscopic anatomical segmentectomy in our department from January 2023 to June 2024 were selected and divided into the ICG fluorescence group(35 cases determining intersegmental plane through ICG fluorescence imaging method)and the modified inflation-deflation group(42 cases determining intersegmental plane through modified inflation-deflation method)according to different methods of determining intersegmental plane.The surgery-related indicators including time of intersegmental plane occurrence,operation time,number of lymph node dissection,postoperative duration of chest tube and postoperative hospital stay as well as the occurrence of complications in the two groups were counted.Patients over 60 years old in two groups were selected and the differences in surgery-related indicators were analyzed.Results The time of intersegmental plane occurrence and operation time in the ICG fluorescence group were shorter than those in the modified inflation-deflation group,with statistically significant differences(P<0.05).There was no significant difference in the number of lymph node dissection,postoperative duration of chest tube or postoperative hospital stay between the two groups(P>0.05).There was no significant difference in the incidence of postoperative complications between the two groups(P>0.05).The time of intersegmental plane occurrence,operation time and postoperative hospital stay of patients over 60 years old in the ICG fluorescence group were shorter than those in the modified inflation-deflation group,with statistically significant differences(P<0.05).Conclusion ICG fluorescence imaging method can display the intersegmental plane clearly and quickly,which can shorten the time of intersegmental plane occurrence and hospital stay in elderly patients with pulmonary nodules.
5.The value of total volume response and total mass response in the therapeutic evaluation of lung metastasis of hepatocarcinoma
Jun-cheng WAN ; Cai-hong YU ; Chang-yu LI ; Yong-jie ZHOU ; Wei ZHANG ; Jian-hua WANG ; Zhi-ping YAN ; Guo-wei YANG ; Zhuo-yang FAN ; Xu-dong QU
Fudan University Journal of Medical Sciences 2025;52(2):201-208,231
Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.
6.Characteristics and factors affecting treatment in hospitalized patients with abnormal uterine bleeding in sub-plateau region
Dan-feng DU ; Ru-juan WANG ; Rong-qun CHA ; Ping JIANG ; Li-qin WANG ; Xi CHEN ; Li-na YANG ; Zhi-yong WU
Fudan University Journal of Medical Sciences 2025;52(3):408-415,423
Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.
7.The value of total volume response and total mass response in the therapeutic evaluation of lung metastasis of hepatocarcinoma
Jun-cheng WAN ; Cai-hong YU ; Chang-yu LI ; Yong-jie ZHOU ; Wei ZHANG ; Jian-hua WANG ; Zhi-ping YAN ; Guo-wei YANG ; Zhuo-yang FAN ; Xu-dong QU
Fudan University Journal of Medical Sciences 2025;52(2):201-208,231
Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.
8.Correlation between D-dimer, antithrombin Ⅲ levels and multiple organ dysfunction syndrome in patients with severe multiple trauma
Kang TOU ; Laifa KONG ; Zhi WANG ; Yong′an XU
Chinese Journal of Postgraduates of Medicine 2025;48(7):577-584
Objective:To explore the correlation between D-dimer (D-D), antithrombin Ⅲ (AT-Ⅲ) at admission, and multiple organ dysfunction syndrome (MODS) in patients with severe multiple trauma.Methods:A retrospective study was conducted to collect data from 80 patients with severe multiple trauma admitted to Jinhua Central Hospital from April 2021 to April 2024. According to the occurrence of MODS within 1 week of treatment, the patients were divided into an occurrence group with 25 cases and a non-occurrence group with 55 cases. The general data, plasma D-D, serum AT-Ⅲ levels and other laboratory indexes at admission were compared between the two groups. The correlation between D-D, AT-Ⅲ at admission and MODS in patients with severe multiple trauma was analyzed.Results:The injury severity rating score (ISS) in the occurrence group was higher than that in the non-occurrence group: (29.12 ± 3.84) points vs. (26.18 ± 3.12) points, the proportion of damage control surgery was lower than that in the non-occurrence group: 32.00% (8/25) vs. 65.45% (36/55), the platelet, AT-Ⅲ and albumin at admission were lower than those in the non-occurrence group: (112.28 ± 20.12) ×10 9/L vs. (123.56 ± 23.47) ×10 9/L, (133.79 ± 18.21) mg/L vs. (148.26 ± 19.57) mg/L, (35.12 ± 6.35) g/L vs. (38.47 ± 5.88) g/L, the D-D at admission was higher than that in the non-occurrence group: (11.36 ± 3.35) mg/L vs. (8.18 ± 2.83) mg/L, and there were statistical differences ( P<0.05). Multivariate Logistic regression analysis result showed that the occurrence of MODS in patients with severe multiple trauma may be related to the ISS at admission, the status of receiving damage control surgery, and the D-D, AT-Ⅲ, albumin at admission ( OR = 1.29, 0.14, 1.34, 0.95 and 0.87; P<0.05). Restrictive cubic spline analysis showed that the risk of MODS in patients with severe multiple trauma showed a non-linear dose-response relationship with D-D and AT-Ⅲ at admission ( P<0.05). When D-D at admission ≥ 9.25 mg/L, the risk of MODS increased with increasing levels, while when AT-Ⅲ at admission ≤ 143.49 mg/L, the risk of MODS increased with decreasing levels. The D-D and AT-Ⅲ at admission had a negative interactive effect on the occurrence of MODS in patients with severe multiple trauma. By drawing decision curves and column charts, it was found that D-D and AT-Ⅲ at admission, as well as other major indicators, had high predictive power for the occurrence of MODS in patients with severe multiple trauma. Conclusions:The occurrence of MODS in patients with severe multiple trauma may be related to the levels of D-D and AT-Ⅲ, and the risk of MODS increases with the increase of D-D and the decrease of AT-Ⅲ at admission. Both can effectively assist other indicators in predicting the risk of MODS in patients.
9.Characteristics and factors affecting treatment in hospitalized patients with abnormal uterine bleeding in sub-plateau region
Dan-feng DU ; Ru-juan WANG ; Rong-qun CHA ; Ping JIANG ; Li-qin WANG ; Xi CHEN ; Li-na YANG ; Zhi-yong WU
Fudan University Journal of Medical Sciences 2025;52(3):408-415,423
Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.
10.Role and mechanism of MANF in inhibition of malignant biological behaviors of gastric cancer cells by rhynchophylline
Li-wei WANG ; Qiang ZHAO ; Da-yong LIU ; Hao ZHENG ; Zhi-gang WEI
Chinese Pharmacological Bulletin 2025;41(12):2326-2333
Aim To investigate the role of mesence-phalic astrocyte-derived neurotrophic factor(MANF)in the inhibitory effect of rhynchophylline(Rhy)on the malignant biological behaviors of gastric cancer cells and its underlying regulatory mechanisms.Meth-ods SGC-7901 gastric cancer cells were transfected using adenovirus and liposome transfection techniques.The experimental groups included:Control group,Rhy group,Rhy+NC group(Rhy+adenovirus-transfected MANF-irrelevant fragment),Rhy+si-MANF group(Rhy+adenovirus-transfected MANF siRNA),Vec-tor group(empty vector),OVE-MANF group(recom-binant plasmid overexpressing MANF).After 24 hours of intervention,cell proliferation,apoptosis,migra-tion,and invasion were assessed using the MTT assay,Hoechst staining,and Transwell assays,respectively.The expressions of MANF,Cyclin D1,and cleaved caspase-3 proteins were measured using Western blot.NF-κB transcriptional activity was evaluated via a lucif-erase reporter assay.Results Compared to the control group,Rhy treatment significantly inhibited gastric cancer cell growth in a dose-dependent manner(P<0.05),induced typical apoptotic morphological chan-ges,and increased the expression of MANF and cleaved caspase-3 proteins(P<0.05),while reduc-ing Cyclin D1 protein expression and NF-κB transcrip-tional activity(P<0.05).Additionally,Rhy treat-ment markedly decreased cell migration and invasion capabilities(P<0.05).In comparison to the Rhy group,adenovirus-mediated transfection of MANF siR-NA suppressed apoptosis,promoted gastric cancer cell proliferation,migration,and invasion,inhibited MANF and cleaved caspase-3 expression(P<0.05),and enhanced Cyclin D1 protein levels and NF-κB transcriptional activity(P<0.05).Compared to the Vector group,OVE-MANF(overexpression of MANF)induced apoptosis,suppressed proliferation,invasion,and metastasis of gastric cancer cells,upregulated MANF and cleaved caspase-3 expression(P<0.05),and inhibited Cyclin D1 protein levels and NF-κB tran-scriptional activity(P<0.05).Conclusion Rhy in-hibits the proliferation,migration,and invasion of gas-tric cancer cells and induces apoptosis,with its mecha-nism linked to the promotion of MANF expression and suppression of NF-κB transcriptional activity.

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