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.

Aim To investigate the high expression of LINC00626 in colorectal cancer,and explore the effects of LINC00626 on the proliferation,apoptosis,and drug sensitivity of colorectal cancer SW480 cells,as well as its underlying mechanisms.Methods Flu-orescence in situ hybridization(FISH)was used to de-tect the expression levels of LINC00626 in 38 colorec-tal cancer tissues and their corresponding adjacent nor-mal tissues.The JASPAR database was utilized to pre-dict co-expressed genes and their possible binding sites.Cell transfection technology was employed to knockdown LINC00626.Western blot and qRT-PCR techniques were used to verify the transfection efficien-cy.CCK-8 assay,cell apoptosis and necrosis staining,and Western blot were used to detect the changes in the proliferation,apoptosis,drug sensitivity,and ap-optotic proteins of SW480 cells,respectively.Results The FISH results indicated that LINC00626 was highly expressed in colorectal cancer tissues(P＜0.05).The expression of LINC00626 was not associat-ed with the age or gender of patients,but was related to the TNM stage and the presence of lymph node me-tastasis($ P＜0.05 $).The results of CCK-8 assay and cell apoptosis and necrosis staining showed that af-ter knockdown of LINC00626,the proliferation ability of SW480 cells decreased,the apoptosis level in-creased,and the drug resistance decreased(P＜0.05).Western blot results showed that with the de-crease in the expression level of LINC00626,the ex-pression of caspase-3 protein decreased,the expression of cleaved caspase-3 protein increased,and the expres-sion of Bcl-2 protein decreased(P＜0.05).Conclu-sions LINC00626 is highly expressed in colorectal cancer and is associated with the TNM stage and the presence of lymph node metastasis.LINC00626 can af-fect the proliferation,apoptosis,and drug sensitivity of SW480 cells and alter the expression of apoptotic pro-teins.

Aim To investigate the expression levels of cytoplasmic FMR1-interacting protein-1(CYFIP1)in colorectal cancer and assess the impact of CYFIP1 interaction on the proliferation and apoptosis of colorec-tal cancer cell HT29,along with its potential mecha-nisms.Methods Immunohistochemistry was em-ployed to assess CYFIP1 expression in 32 colorectal cancer tissues and adjacent tissues.Coexpressed genes were identified using the GEPIA2 website to predict potential correlations and binding sites.Following the construction of a siRNA-CYFIP1,alterations in cell proliferation,apoptosis,and levels of apoptosis-related proteins were evaluated through CCK-8 assay,Hoechst 33342/PI double staining assay,and Western blot a-nalysis,respectively.Results The immunohisto-chemical findings revealed a significantly elevated level of CYFIP1 expression in colorectal cancer tissues com-pared to paracancer tissues(P＜0.05).The expres-sion of CYFIP1 did not show any correlation with age and gender,but exhibited associations with TNM stage and lymph node metastasis(P＜0.05).A conserved TP53 binding site was predicted in the 3kbps DNA re-gion upstream of the CYFIP1 gene using GEPIA2,JASPAR databases,and rVista 2.0 promoter prediction software.Following transfection of HT29 cells with siRNA-CYFIP1,the clonogenesis and proliferation of cells significantly decreased(P＜0.05).Additional-ly,the levels of cleaved caspase-3 were elevated,while the expression levels of caspase-3 and Bcl-2 were reduced after transfection with siRNA-CYFIP1(P＜0.05),which might be related to the interaction be-tween CYFIP1 and TP53.Conclusions The upregu-lation of CYFIP1 in colorectal cancer is associated with TNM stage and lymph node metastasis.Upon silen-cing,CYFIP1 demonstrates the ability to suppress pro-liferation in HT29 cells and modulate the expression of apoptotic proteins.

Gefitinib,a first-generation epidermal growth factor receptor(EGFR)tyrosine kinase inhibi-tor(TKI),exerts significant therapeutic efficacy in the treatment of non-small cell lung cancer(NSCLC)by selectively targeting mutant forms of EGFR.However,the development of acquired resistance signifi-cantly limits its long-term clinical benefits.Cell division cycle 20(CDC20),a key regulator of cell cycle progression,has been implicated in the tumorigenesis and progression of various malignancies.Neverthe-less,its role and underlying regulatory mechanisms in the acquisition of drug resistance in NSCLC remain largely unexplored.This study aimed to elucidate the molecular mechanisms by which CDC20 contributes to gefitinib resistance in NSCLC.Gefitinib-resistant cell lines,HCC827/GR(ICs0 0.05±0.01 μmnol/L vs 36.24±6.21 μmol/L)and PC9/GR(IC50 0.02±0.01 μmol/L vs 25.36±5.57 μmol/L),were established through stepwise drug induction,exhibiting markedly increased IC50 values compared to their parental counterparts.Bioinformatics analysis revealed that the transcriptional level of CDC20 is signifi-cantly upregulated in lung cancer tissues and is associated with poor patient prognosis.Western blotting analysis confirmed elevated CDC20 protein levels in the resistant HCC827/GR and PC9/GR cells relative to the parental HCC827 and PC9 cells.To further investigate the functional role of CDC20 in NSCLC ge-fitinib resistance,CDC20 was knocked out using CRISPR/Cas9 technology.This genetic intervention sig-nificantly restored gefitinib sensitivity in resistant cells(IC 50 37.08±6.15 μmol/L vs 10.49±1.83μmol/L,7.23±1.55 μamol/L),while concurrently promoting apoptosis and inducing G2/M phase cell cycle arrest.Conversely,CDC20 overexpression decreased drug sensitivity in parental cells and notably attenuated gefitinib-induced apoptosis and cell cycle arrest.Mechanistically,CDC20 depletion was found to inhibit activation of the PI3K/Akt/mTOR signaling pathway,upregulate pro-apoptotic proteins such as cleaved-Caspase 3 and Bax,and downregulate the anti-apoptotic protein Bcl-2.Collectively,these find-ings demonstrate that CDC20 mediates gefitinib resistance in NSCLC through modulation of the PI3K/Akt/mTOR signaling pathway,thereby identifying CDC20 as a potential therapeutic target for overcoming resistance to EGFR-targeted therapies.

Gefitinib,a first-generation epidermal growth factor receptor(EGFR)tyrosine kinase inhibi-tor(TKI),exerts significant therapeutic efficacy in the treatment of non-small cell lung cancer(NSCLC)by selectively targeting mutant forms of EGFR.However,the development of acquired resistance signifi-cantly limits its long-term clinical benefits.Cell division cycle 20(CDC20),a key regulator of cell cycle progression,has been implicated in the tumorigenesis and progression of various malignancies.Neverthe-less,its role and underlying regulatory mechanisms in the acquisition of drug resistance in NSCLC remain largely unexplored.This study aimed to elucidate the molecular mechanisms by which CDC20 contributes to gefitinib resistance in NSCLC.Gefitinib-resistant cell lines,HCC827/GR(ICs0 0.05±0.01 μmnol/L vs 36.24±6.21 μmol/L)and PC9/GR(IC50 0.02±0.01 μmol/L vs 25.36±5.57 μmol/L),were established through stepwise drug induction,exhibiting markedly increased IC50 values compared to their parental counterparts.Bioinformatics analysis revealed that the transcriptional level of CDC20 is signifi-cantly upregulated in lung cancer tissues and is associated with poor patient prognosis.Western blotting analysis confirmed elevated CDC20 protein levels in the resistant HCC827/GR and PC9/GR cells relative to the parental HCC827 and PC9 cells.To further investigate the functional role of CDC20 in NSCLC ge-fitinib resistance,CDC20 was knocked out using CRISPR/Cas9 technology.This genetic intervention sig-nificantly restored gefitinib sensitivity in resistant cells(IC 50 37.08±6.15 μmol/L vs 10.49±1.83μmol/L,7.23±1.55 μamol/L),while concurrently promoting apoptosis and inducing G2/M phase cell cycle arrest.Conversely,CDC20 overexpression decreased drug sensitivity in parental cells and notably attenuated gefitinib-induced apoptosis and cell cycle arrest.Mechanistically,CDC20 depletion was found to inhibit activation of the PI3K/Akt/mTOR signaling pathway,upregulate pro-apoptotic proteins such as cleaved-Caspase 3 and Bax,and downregulate the anti-apoptotic protein Bcl-2.Collectively,these find-ings demonstrate that CDC20 mediates gefitinib resistance in NSCLC through modulation of the PI3K/Akt/mTOR signaling pathway,thereby identifying CDC20 as a potential therapeutic target for overcoming resistance to EGFR-targeted therapies.

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.

Aim To investigate the high expression of LINC00626 in colorectal cancer,and explore the effects of LINC00626 on the proliferation,apoptosis,and drug sensitivity of colorectal cancer SW480 cells,as well as its underlying mechanisms.Methods Flu-orescence in situ hybridization(FISH)was used to de-tect the expression levels of LINC00626 in 38 colorec-tal cancer tissues and their corresponding adjacent nor-mal tissues.The JASPAR database was utilized to pre-dict co-expressed genes and their possible binding sites.Cell transfection technology was employed to knockdown LINC00626.Western blot and qRT-PCR techniques were used to verify the transfection efficien-cy.CCK-8 assay,cell apoptosis and necrosis staining,and Western blot were used to detect the changes in the proliferation,apoptosis,drug sensitivity,and ap-optotic proteins of SW480 cells,respectively.Results The FISH results indicated that LINC00626 was highly expressed in colorectal cancer tissues(P＜0.05).The expression of LINC00626 was not associat-ed with the age or gender of patients,but was related to the TNM stage and the presence of lymph node me-tastasis($ P＜0.05 $).The results of CCK-8 assay and cell apoptosis and necrosis staining showed that af-ter knockdown of LINC00626,the proliferation ability of SW480 cells decreased,the apoptosis level in-creased,and the drug resistance decreased(P＜0.05).Western blot results showed that with the de-crease in the expression level of LINC00626,the ex-pression of caspase-3 protein decreased,the expression of cleaved caspase-3 protein increased,and the expres-sion of Bcl-2 protein decreased(P＜0.05).Conclu-sions LINC00626 is highly expressed in colorectal cancer and is associated with the TNM stage and the presence of lymph node metastasis.LINC00626 can af-fect the proliferation,apoptosis,and drug sensitivity of SW480 cells and alter the expression of apoptotic pro-teins.

Objective:To explore the dosimetry optimization strategy based on filter thickness and shape selection for the bulb superficial X-ray radiotherapy unit.Methods:Monte Carlo code TOPAS was used to model tubular equipment, and the dose distribution from six X-ray energies (50-150 kV) and five conventional aluminum filters (0.5-3.0 mm) with different thickness were simulated in the water model. The percentage depth dose (PDD) curve along the central axis, the center-axis profile dose at different depths, and the lateral dose distribution were analyzed. The dose distribution of three different designs of aluminum filters (conventional cylindrical, conical and oblique cylindrical filters) was compared to evaluate the effect of dosimetric optimization of different filter shapes.Results:Under the same energy, increasing the thickness of the filter can optimize the superficial skin dose, and the optimization effect of depth dose uniformity can be increased by 26% at a depth of 5.5 mm at 70 kV energy. The raised, flat and inclined dose distribution modes can be achieved by using conventional cylindrical, conical and inclined aluminum filters.Conclusions:By selecting the appropriate X-ray energy and filter thickness, an ideal dose distribution matching the tumor depth can be achieved. The application of personalized filters is also of great significance for diverse target areas.

Aim To investigate the expression levels of cytoplasmic FMR1-interacting protein-1(CYFIP1)in colorectal cancer and assess the impact of CYFIP1 interaction on the proliferation and apoptosis of colorec-tal cancer cell HT29,along with its potential mecha-nisms.Methods Immunohistochemistry was em-ployed to assess CYFIP1 expression in 32 colorectal cancer tissues and adjacent tissues.Coexpressed genes were identified using the GEPIA2 website to predict potential correlations and binding sites.Following the construction of a siRNA-CYFIP1,alterations in cell proliferation,apoptosis,and levels of apoptosis-related proteins were evaluated through CCK-8 assay,Hoechst 33342/PI double staining assay,and Western blot a-nalysis,respectively.Results The immunohisto-chemical findings revealed a significantly elevated level of CYFIP1 expression in colorectal cancer tissues com-pared to paracancer tissues(P＜0.05).The expres-sion of CYFIP1 did not show any correlation with age and gender,but exhibited associations with TNM stage and lymph node metastasis(P＜0.05).A conserved TP53 binding site was predicted in the 3kbps DNA re-gion upstream of the CYFIP1 gene using GEPIA2,JASPAR databases,and rVista 2.0 promoter prediction software.Following transfection of HT29 cells with siRNA-CYFIP1,the clonogenesis and proliferation of cells significantly decreased(P＜0.05).Additional-ly,the levels of cleaved caspase-3 were elevated,while the expression levels of caspase-3 and Bcl-2 were reduced after transfection with siRNA-CYFIP1(P＜0.05),which might be related to the interaction be-tween CYFIP1 and TP53.Conclusions The upregu-lation of CYFIP1 in colorectal cancer is associated with TNM stage and lymph node metastasis.Upon silen-cing,CYFIP1 demonstrates the ability to suppress pro-liferation in HT29 cells and modulate the expression of apoptotic proteins.

Objective:This study aimed to investigate the association between anemia and hypothyroidism during early pregnancy.Methods:We conducted a retrospective analysis of 3,165 pregnant women who registered at Qingdao Women and Children's Hospital from April 2021 to March 2022.Participants were categorized into a hypothyroidism group(n=177)and a euthyroid control group(n=2 988).Maternal demographic data,anemia-related markers(hemoglobin,Hb),and thyroid function parameters(FT3,FT4,TSH)were collected.Statistical analyses included independent t-tests,chi-square tests,Spearman correlation,and multivariate logistic regression.Results:The hypothyroidism group exhibited a significantly higher anemia incidence(10.17%vs 5.02%,P<0.05)and lower mean Hb levels(122.70±10.19 g/L vs 124.60±9.19 g/L,P<0.05)compared to controls.Spearman analysis revealed positive correlations between Hb and FT3(r=0.176)and FT4(r=0.051)(both P<0.05).Multivariate logistic regression identified anemia as an independent risk factor for hypothyroidism(OR=2.038,95%CI:1.202～3.455,P=0.008).Conclusion:Anemia in early pregnancy is associated with the risk of hypothyroidism.We recommend enhanced thyroid function screening and early intervention for anemic pregnant women to mitigate potential complications.