OBJECTIVE To analyze the efficacy and safety of luspatercept in the treatment of myelodysplastic syndromes （MDS） anemia， and provide reference for clinical medication. METHODS The literature related to luspatercept for MDS anemia in PubMed， Cochrane Library， Embase and Web of Science were searched by computer， and the search time was from the establishment of the database to January 2024. The quality of literature was evaluated after they were screened according to inclusion and exclusion criteria， the single-group rate meta-analysis and sensitivity analysis were performed by using RevMan 5.4 software， and the subgroup analysis was conducted. RESULTS A total of 756 patients in 9 articles were included in this study. The results of meta-analysis showed that the proportion of MDS patients who reached ≥8 weeks of red blood cell transfusion independence （RBC-TI） was 46% after using luspatercept [95%CI （0.28， 0.64）， P＜0.000 01]. The proportion of MDS patients whose hematological improvement in erythrocyte （HI-E） was 59% [95%CI （0.43， 0.74）， P＜0.000 01]. Among them， 5 articles reported that the proportion of MDS patients with grade 3-4 adverse reactions was 14% [95%CI （0.07， 0.22）， P＝0.000 2]， and the poor general condition， infection， blood and lymphatic system disease were the common adverse reactions. Subgroup analysis showed that the source of heterogeneity was the blood transfusion burden in the proportion of MDS patients with RBC-TI≥8 weeks， and the source of heterogeneity was the 0931-8356251。revised international prognostic scoring system （IPSS-R） risk grade， SF3B1 mutation status and blood transfusion burden in the proportion of MDS patients with HI-E. Sensitivity analysis showed that the results of this study were stable. CONCLUSIONS Luspatercept can significantly improve blood transfusion dependence， reduce blood transfusion burden and promote hematology improvement in MDS patients. But attention should be paid to the occurrence of grade 3-4 adverse events； adverse events such as poor general condition， infection， blood and lymphatic system diseases are more common.

Objective To investigate the impact of nucleophosmin 1-mutated(NPM1m)subtypes,variant allele frequency(VAF)and co-mutations on the survival outcomes of patients with acute myeloid leukemia(AML).Methods Clinical data,mutation status,and outcomes of 86 NPM1m-AML patients admitted in Department of Hematology,First Hospital of Lanzhou University between June 2017 and September 2024 were collected and retrospectively analyzed.Spearman correlation analysis,Kaplan-Meier curve analysis,Log-rank test,and Cox regression analysis was applied for correlation analysis,survival analysis,and factors affecting survival.Results The overall survival(OS)was significantly shorter in the Rares subtype of NPM1m than the ABD subtype(median OS:164 d vs 416 d,P=0.043).The VAF of NPM1m was positively correlated with the initial peripheral blood white blood cell count and lactate dehydrogenase(LDH)level(P<0.05).OS was reduced when VAF was≥0.37(median OS:164 d vs 730 d,P=0.003).The presence of myelodysplasia-related gene(MR)mutations was associated with a poorer prognosis when compared to the MR wild-type(median OS:45 d vs 395 d,P<0.001).The triple mutation of FMS-like tyrosine kinase 3-internal tandem duplication(FLT3-ITD)and DNMT3A also indicated a worse prognosis than the non-triple mutation(median OS:173 d vs 483 d,P=0.007).The presence of PTPN11 mutations was associated with improved OS(median OS:395 d vs 240 d,P=0.027),while the patients with coexistence of N/KRAS mutations trended toward better prognosis than the wild-type patients(median OS:662 d vs 189 d)though no statistical significance(P=0.070).Multivariate analysis revealed that LDH(HR=1.002,95%CI:1.000～1.003,P=0.005),NPM1m VAF(HR=2.415,95%CI:1.208～4.829,P=0.013),Rares subtype(HR=3.037,95%CI:1.134～8.136,P=0.027),and MR mutations(HR=5.283,95%CI:1.991～14.017,P<0.001)were independent risk factors associated with OS in the patients.Conclusion Molecular heterogeneity of NPM1m should be taken into account in prognostic stratification of NPM1m-AML.Factors including the Rares subtype,VAF≥0.37,coexistence of FLT3-ITD and DNMT3A mutations,and MR mutations are associated with poor prognosis of NPM1m-AML.The presence of PTPN11 mutations improves the prognosis,while the presence of N/KRAS mutations shows a trend toward better prognosis.LDH,NPM1m VAF,Rares subtype,and MR mutations are independent risk factors affecting OS of patients with NPM1m-AML.

The nucleophosmin 1(NPM1)muta-tion is one of the most frequent subtypes in acute myeloid leukemia(AML).Under the conditions of FLT3-internal tandem duplications(FLT3-ITD)and/or DNMT3A co-mutations or adverse cytogenetics,the originally favorable prognosis will deteriorate.In recent years,studies have found that multiple endocrine neoplasia protein(Menin)inhibitors tar-geting Menin-KMT2A complex can downregulate the overexpression of leukemia causing genes HOX(homeotic gene)and MEIS1(myeloid ecotropic vi-ral integration site 1)in NPM1-mutated AML,dem-onstrating remarkable anti-leukemia activity.This article aims to review the mechanism and clinical research of Menin inhibitors,novel small molecule targeted drugs in NPM1-mutated AML,as well as the resistance mechanism of Menin inhibitors,hop-ing to provide promising approaches for the subse-quent treatment of NPM1-mutated AML patients.

The nucleophosmin 1(NPM1)muta-tion is one of the most frequent subtypes in acute myeloid leukemia(AML).Under the conditions of FLT3-internal tandem duplications(FLT3-ITD)and/or DNMT3A co-mutations or adverse cytogenetics,the originally favorable prognosis will deteriorate.In recent years,studies have found that multiple endocrine neoplasia protein(Menin)inhibitors tar-geting Menin-KMT2A complex can downregulate the overexpression of leukemia causing genes HOX(homeotic gene)and MEIS1(myeloid ecotropic vi-ral integration site 1)in NPM1-mutated AML,dem-onstrating remarkable anti-leukemia activity.This article aims to review the mechanism and clinical research of Menin inhibitors,novel small molecule targeted drugs in NPM1-mutated AML,as well as the resistance mechanism of Menin inhibitors,hop-ing to provide promising approaches for the subse-quent treatment of NPM1-mutated AML patients.

Objective:To investigate the heterogeneity of FLT3 mutations and the consequences of co-occurring mutations on the clinical features and prognosis of patients with acute myeloid leukemia(AML).Methods:We retrospectively analyzed the clinical characteristics of 80 patients with AML who carried FLT3 mutations,as detected by genetic testing,and were treated in The First Hospital of Lanzhou Uni-versity from October 2017 to March 2024.An analysis was performed to evaluate the impact of FLT3 mutation frequency,insertion length of base pairs,insertion site,and co-occurring mutations on survival outcomes.Results:The variant allele frequency(VAF)of FLT3-ITD muta-tions was correlated with leukocyte counts and lactate dehydrogenase levels in patients with de novo AML.There was an association between the insertion site and the length of the base-pair insertion.Patients with AML who also had a VAF of FLT3-ITD mutations greater than or equal to 0.38 exhibit reduced overall survival(OS),whereas the length of base pair insertion,insertion site,and number of muta-tions did not correlate with OS.Patients with non-classical FLT3 mutations demonstrated a significantly longer OS than did those with FLT3-ITD mutations.The co-occurrence of FLT3-ITD,NPM1,and DNMT3A mutations was associated with markedly reduced OS.The use of FLT3 inhibitors and allogeneic hematopoietic stem cell transplantation(allo-HSCT)can improve the prognosis of patients with FLT3-ITD mutations.Conclusions:FLT3 mutational heterogeneity correlates with the clinical characteristics and outcomes of patients with AML.Non-classical FLT3 and FLT3-TKD mutations are associated with superior prognosis.Patients with a VAF of 0.38 or higher have a poorer prognosis,but the use of FLT3 inhibitors can improve their prognosis.Patients with triple mutations have poor prognosis.

Myelodysplastic syndrome(MDS)is a heterogeneous myeloid tumor that originates from hematopoietic stem cells(HSCs)and is associated with a high risk of progression to acute myeloid leukemia(AML).Studies have shown that 90%of patients with MDS have gene mutations,of whom approximately 25%have SF3B1 mutations.In patients with MDS carrying this mutation,the TGF-β pathway is upregu-lated,inducing cell cycle arrest and thereby leading to erythroid ineffective hematopoiesis and pathological hematopoiesis.Luspatercept can be used as a ligand trap to capture TGF-β ligands,inhibit SMAD2/3 pathway activation,downregulate TGF-β pathway,and promote ad-vanced red blood cell maturation.Currently,it has been approved by the Food and Drug Administration(FDA)for the treatment of anemia in patients with low-risk MDS,and studies have shown that the response rate is higher in patients with SF3B1 mutations.This article will re-view the current status of luspatercept in the treatment of SF3B1 mutation-related MDS;it will also analyze its effectiveness and safety and provide therapeutic strategies for clinical use.

Objective:To investigate the heterogeneity of FLT3 mutations and the consequences of co-occurring mutations on the clinical features and prognosis of patients with acute myeloid leukemia(AML).Methods:We retrospectively analyzed the clinical characteristics of 80 patients with AML who carried FLT3 mutations,as detected by genetic testing,and were treated in The First Hospital of Lanzhou Uni-versity from October 2017 to March 2024.An analysis was performed to evaluate the impact of FLT3 mutation frequency,insertion length of base pairs,insertion site,and co-occurring mutations on survival outcomes.Results:The variant allele frequency(VAF)of FLT3-ITD muta-tions was correlated with leukocyte counts and lactate dehydrogenase levels in patients with de novo AML.There was an association between the insertion site and the length of the base-pair insertion.Patients with AML who also had a VAF of FLT3-ITD mutations greater than or equal to 0.38 exhibit reduced overall survival(OS),whereas the length of base pair insertion,insertion site,and number of muta-tions did not correlate with OS.Patients with non-classical FLT3 mutations demonstrated a significantly longer OS than did those with FLT3-ITD mutations.The co-occurrence of FLT3-ITD,NPM1,and DNMT3A mutations was associated with markedly reduced OS.The use of FLT3 inhibitors and allogeneic hematopoietic stem cell transplantation(allo-HSCT)can improve the prognosis of patients with FLT3-ITD mutations.Conclusions:FLT3 mutational heterogeneity correlates with the clinical characteristics and outcomes of patients with AML.Non-classical FLT3 and FLT3-TKD mutations are associated with superior prognosis.Patients with a VAF of 0.38 or higher have a poorer prognosis,but the use of FLT3 inhibitors can improve their prognosis.Patients with triple mutations have poor prognosis.

Objective:To compare the ability of deep convolutional neural network-crop (DCNN-C) and deep convolutional neural network-whole (DCNN-W), 2 artificial intelligence systems based on different training methods to dignose early gastric cancer (EGC) diagnosis under magnifying image-enhanced endoscopy (M-IEE).Methods:The images and video clips of EGC and non-cancerous lesions under M-IEE under narrow band imaging or blue laser imaging mode were retrospectively collected in the Endoscopy Center of Renmin Hospital of Wuhan University, for the training set and test set for DCNN-C and DCNN-W. The ability of DCNN-C and DCNN-W in EGC identity in image test set were compared. The ability of DCNN-C, DCNN-W and 3 senior endoscopists (average performance) in EGC identity in video test set were also compared. Paired Chi-squared test and Chi-squared test were used for statistical analysis. Inter-observer agreement was expressed as Cohen′s Kappa statistical coefficient (Kappa value).Results:In the image test set, the accuracy, sensitivity, specificity and positive predictive value of DCNN-C in EGC diagnosis were 94.97%(1 133/1 193), 97.12% (202/208), 94.52% (931/985), and 78.91%(202/256), respectively, which were higher than those of DCNN-W(86.84%, 1 036/1 193; 92.79%, 193/208; 85.58%, 843/985 and 57.61%, 193/335), and the differences were statistically significant ( χ2=4.82, 4.63, 61.04 and 29.69, P=0.028, =0.035, <0.001 and <0.001). In the video test set, the accuracy, specificity and positive predictive value of senior endoscopists in EGC diagnosis were 67.67%, 60.42%, and 53.37%, respectively, which were lower than those of DCNN-C (93.00%, 92.19% and 87.18%), and the differences were statistically significant ( χ2=20.83, 16.41 and 11.61, P<0.001, <0.001 and =0.001). The accuracy, specificity and positive predictive value of DCNN-C in EGC diagnosis were higher than those of DCNN-W (79.00%, 70.31% and 64.15%, respectively), and the differences were statistically significant ( χ2=7.04, 8.45 and 6.18, P=0.007, 0.003 and 0.013). There were no significant differences in accuracy, specificity and positive predictive value between senior endoscopists and DCNN-W in EGC diagnosis (all P>0.05). The sensitivity of senior endoscopists, DCNN-W and DCNN-C in EGC diagnosis were 80.56%, 94.44%, and 94.44%, respectively, and the differences were not statistically significant (all P>0.05). The results of the agreement analysis showed that the agreement between senior endoscopists and the gold standard was fair to moderate (Kappa=0.259, 0.532, 0.329), the agreement between DCNN-W and the gold standard was moderate (Kappa=0.587), and the agreement between DCNN-C and the gold standard was very high (Kappa=0.851). Conclusion:When the training set is the same, the ability of DCNN-C in EGC diagnosis is better than that of DCNN-W and senior endoscopists, and the diagnostic level of DCNN-W is equivalent to that of senior endoscopists.

Objective:To develop early gastric cancer (EGC) detection system of magnifying blue laser imaging (ME-BLI) model and magnifying narrow-band imaging (ME-NBI) model based on deep convolutional neural network, to compare the performance differences of the two models and to explore the effects of training methods on the accuracy.Methods:The images of benign gastric lesions and EGC under ME-BLI and ME-NBI were respectively collected. A total of five data sets and three test sets were collected. Data set 1 included 2 024 noncancerous lesions and 452 EGC images under ME-BLI. Data set 2 included 2 024 noncancerous lesions and 452 EGC images under ME-NBI. Data set 3 was the combination of data set 1 and 2 (a total of 4 048 noncancerous lesions and 904 EGC images under ME-BLI and ME-NBI). Data set 4: on the basis of data set 2, another 62 noncancerous lesions and 2 305 EGC images under ME-NBI were added (2 086 noncancerous lesions and 2 757 EGC images under ME-NBI). Data set 5: on the basis of data set 3, another 62 noncancerous lesions and 2 305 EGC images under ME-NBI were added(4 110 noncancerous lesions and 3 209 EGC images under ME-NBI and ME-BLI). Test set A included 422 noncancerous lesions and 197 EGC images under ME-BLI. Test set B included 422 noncancerous lesions and 197 EGC images under ME-NBI. Test set C was the combination of test set A and B (844 noncancerous and 394 EGC images under ME-BLI and ME-NBI). Five models were constructed according to these five data sets respectively and their performance was evaluated in the three test sets. Per-lesion video was collected and used to compare the performance of deep convolutional neural network models under ME-BLI and ME-NBI for the detection of EGC in clinical environment, and compared with four senior endoscopy doctors. The primary endpoint was the diagnostic accuracy of EGG, sensitivity and specificity. Chi-square test was used for statistical analysis.Results:The performance of model 1 was the best in test set A with the accuracy, sensitivity and specificity of 76.90% (476/619), 63.96% (126/197) and 82.94% (350/422), respectively. The performance of model 2 was the best in test set B with the accuracy, sensitivity and specificity of 86.75% (537/619), 92.89% (183/197) and 83.89% (354/422), respectively. The performance of model 3 was the best in test set B with the accuracy, sensitivity and specificity of 86.91% (538/619), 84.26% (166/197) and 88.15% (372/422), respectively. The performance of model 4 was the best in test set B with the accuracy, sensitivity and specificity of 85.46% (529/619), 95.43% (188/197) and 80.81% (341/422), respectively. The performance of model 5 was the best in test set B, with the accuracy, sensitivity and specificity of 83.52% (517/619), 96.95% (191/197) and 77.25% (326/422), respectively. In terms of image recognition of EGC, the accuracy of models 2 to 5 was higher than that of model 1, and the differences were statistically significant ( χ2=147.90, 149.67, 134.20 and 115.30, all P<0.01). The sensitivity and specificity of models 2 and 3 were higher than those of model 1, the specificity of model 2 was lower than that of model 3, and the differences were statistically significant ( χ2=131.65, 64.15, 207.60, 262.03 and 96.73, all P < 0.01). The sensitivity of models 4 and 5 was higher than those of models 1 to 3, and the specificity of models 4 and 5 was lower than those of models 1 to 3, and the differences were statistically significant ( χ2=151.16, 165.49, 71.35, 112.47, 132.62, 153.14, 176.93, 74.62, 14.09, 15.47, 6.02 and 5.80, all P<0.05). The results of video test based on lesion showed that the average accuracy of doctors 1 to 4 was 68.16%. And the accuracy of models 1 to 5 was 69.47% (66/95), 69.47% (66/95), 70.53% (67/95), 76.84% (73/95) and 80.00% (76/95), respectively. There were no significant differences in the accuracy among models 1 to 5 and between models 1 to 5 and doctors 1 to 4 (all P>0.05). Conclusions:ME-BLI EGC recognition model based on deep learning has good accuracy, but the diagnostic effecacy is sligntly worse than that of ME-NBI model. The effects of EGC recognition model of ME-NBI combined with ME-BLI is better than that of a single model. A more sensitive ME-NBI model can be obtained by increasing the number of ME-NBI images, especially the images of EGG, but the specificity is worse.

Objective To study the effects of knock down midkine(MK)by siRNA on chemosinsitivity in bladder cancer cells. Methods Three MK siRNAs were designed and constructed. After transfected with MK siRNA or scrambled siRNA for different time, cultured cells were harvested to carry on the next experiments. Expression of MK was determined by real-time RT-PCR and western blot, and apoptosis were evaluated by caspase-3 activity and TUNEL assay. MTT was performed to examine the inhibition effect of Paclitaxel (PTX) on cells. Results MK siRNA could down-regulate the MK expression in a dose- and time-dependent manner. The MTT results showed that the inhibit rates were (18.21±0.36)%, (18.19±0.29)%, (17.89±0.33)%, (1.86±0.52)%, (32.56±0.53) %, (53. 83±0.38) % and (78. 95±0.55) % in different groups PTX alone(0.2μmol/L), ConA +PTX(0.2 μmol/L), Con-B +PTX(0.2 μmol/L), siRNA alone(12. 50 nmol/L), siRNA(3. 125nmol/L) + PTX (0. 2 μmol/L), siRNA (6. 25 nmol/L) + PTX (0. 2 μmol/L) and siRNA (12. 50nmol/L)+PTX(0.2 μmol/L), respectively. The TUNEL results showed that apoptosis index was (1.81 ±0. 36)%, (1. 89±0. 38)%, (5. 56±0. 58)%, (9. 68±0.55)% and (15. 25±0.56)% in different groups (Con-A, Con-B, siRNA (3. 125 nmol/L), siRNA (6. 25 nmol/L) and siRNA ( 12. 5nmol/L), respectively. The activity of caspase-3 increased significantly in transefected cells with a dose-and time-dependent manner. Conclusion MK siRNA could sensitize human bladder cancer cells to chemotherapy which might be through the apotosis.