Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Objective: Summarize the anatomical features of the aortic dissection of right axillary and femoral artery cannulation in Sun's surgery. Exploring whether right axillary and femoral artery cannulation can reduce the incidence of organ malperfusion and improve patient prognosis. Methods: From January 2015 to December 2017, 181 cases with aortic dissection were treated in Beijing Anzhen Hospital affiliated to Capital Medical University, Beijing Great Blood Vessel Research and Treatment Center, 122 patients were enrolled in the right axillary and femoral artery cannulation group, and 59 patients in control group were enrolled. Retrospective analysis the data of two groups, intraoperative, and postoperative univariate were compared between the two groups. Results: A total of 17 patients died in the postoperative group, with 9 (7.38%) in the combined perfusion group and 8 (13.56%) in the control group, P=0.181. Among the complications of the two groups, 18 patients(14.75%) in combined perfusion group had renal insufficiency and 17 patients (28.81%) in the control group, P= 0.025. 0 case had stransient spinal cord injury in combined perfusion group , 3 cases(5.08%) in control group , P=0.033. Conclusion Right axillary and femoral artery cannulation can reduce the incidence of complications of postoperative organ dysfunction and improve patient prognosis.

Objective To investigate the correlations between the FBN1 gene mutation types and the clinical phenotype . Methods 87 probands with Marfan or Marfan-like syndromes and their family members were enrolled in this study ( total 300 cases).The clinical manifestations of each patients involving the ocular, cardiovascular system, skeletal system and other im-plicated systems were collected and evaluated .According to the clinical manifestations , these patients were divided into two groups, namely aortic dissection group and aortic root aneurysm group.Blood samples were taken from patients and DNA se-quencing was performed on each patient by the genetic aortic disease gene Panel .The detected single nucleotide variants ( SNVs)/indel were interpreted according to the ACMG guidelines, and the pathogenic variation was confirmed through Sanger sequencing.The aortic wall tissue was obtained from MFS patients who underwent surgery .The correlations between genotypes and clinical phenotypes were further explored by comparing the aortic wall tissue histological specimens of each genotype pa-tient.Results A total of 92 FBN1 mutations(31％) were detected in 300 people with Marfan syndromes or Marfan-like syn-dromes, 18 of which were undiscovered mutations.There were 49 missense mutations(53.26％), 13 splicing mutations (14.13％), 17 frameshift mutations(18.48％), and 13 nonsense mutations(14.13％).In this cohort, 24 cases had aortic dissection and 25 cases were aortic root aneurysm.Statistical analysis revealed that patients with aortic dissection mostly ap-peared in frameshift mutations(29.17％ vs.4.00％, P =0.017).However, patients with aortic root aneurysm mostly ap-peared in missense mutations(72.00％ vs.37.50％, P =0.015), and accompanied with ectopia lentis(41.67％ vs. 8.33％, P=0.008).Pathological specimens staining found that elastic fibers in the aortic wall of patients with frameshift mu-tations are sparser, and the smooth muscle cells are more deficient and more disorganized than patients with missense muta-tions.Conclusion FBN1 gene frameshift mutations result a lack of elastic fibers and disorganized smooth muscle cells in aor-tic wall and are presented more in patients with aortic dissection than aortic root aneurysm .

Objective To detect the expression of stem cell marker Sox2 in gastric cancer (GC). Methods The mRNA and protein expressions of Sox2 in paired primary tumor tissues and their matching, adjacent non-cancerous tissues in a series of 60 cases of human GC were examined by reverse transcription-PCR (RT-PCR) and immunohistochemistry (IHC). χ2 test was used to analyze the correlation of Sox2 expression with clinicopathological parameters of GC tissues including age, gender, tumor size, histological type, TNM stage, differentiation degree, depth of invasion and lymph node metastasis. Results RT-PCR results showed that the positive rate of Sox2 expression was significantly increased in gastric tumor tissues (53.3%, 32/60) compared with that of matching, adjacent non-cancerous tissues (20.0%, 12/60, P<0.01). Semi-quantitative analysis showed that the relative intensity of Sox2 mRNA expression was significantly higher in gastric cancer tissues (0.724±0.209) than that in tissues adjacent to carcinoma (0.256±0.065,P<0.01). The positive expression of Sox2 was significantly higher in gastric tumor tissues (50.0%, 30/60) than that of matching, adjacent non-cancerous tissues (16.7%, 10/60,P<0.01). The positive expression of Sox2 was significantly higher in gastric tumor patients with TNM stage (Ⅲ+Ⅳ) than that of TNM stage (Ⅰ+Ⅱ). The positive expression of Sox2 was significantly higher in gastric tumor patients with low differentiation and undifferentiated tumor cells than that of patients with middle and high differented cells. The positive expression of Sox2 was also significantly higher in gastric tumor patients with the depth of invasion T3-T4 than that of patients with T1-T2. The positive expression of Sox2 was significantly higher in gastric tumor patients with lymph node metastasis than that of patients without lymph node metastasis (P<0.05 or P<0.01). Conclusion The elevated expression of Sox2 is associated with the initiation, invasion, progression, and metastasis of GC. Sox2 may serve as a novel diagnostic and therapeutic marker for human GC.

Objective To investigate the feasibility and value of CT perfusion imaging in combination of CTA 320-slice CT with dual-low-dose in detection of acute cerebral ischemia.Methods Forty patients with acute stroke underwent perfusion imaging and CTA using a single scan with 320-slice CT with dual-low-dose schedule.CTA,4D-CTA,4D-perfusion imaging and fusion images were generated at a post-processing workstation.All patients also underwent a 3.0T magnetic resonance imaging with DWI for a comparison.Quality of the images,degree of vascular stenosis,and location of ischemic lesions were evaluated.Results The vascu-lar stenosis or occlusion was found in 33 patients,8 of whom were confirmed by the DSA.The ratio of better images of CTA was 82.5%.CTP showed 297 lesions with abnormal perfusion.202 lesions were confirmed as infarct by DWI,while 95 ones were nor-mal on DWI but with increased DLY and TTP and slightly decreased CBF and CBV in 49,increased DLY and TTP and normal CBF and CBV in 21,and increased DLY and TTP and slightly increased CBF and CBV in 25.Conclusion CT perfusion in combination with CTA by 320-slice CT with dual-low-dose is feasible and useful to observe accurately the vascular structures and the ischemic status of the whole brain at early stage.

Objective By comparing the effects of different combined therapy,to explore the best therapy in prevention of intrauterine adhesions (IUA)after Transcervical resection of adhesions (TCRA).Methods Eighty patents with serious or moderate IUA were randomly divided into four groups.Group A:Artificial cycle combined with ball pouch,sodium hyaluronate gel.Group B:artificial cycle combined with intrauterine device(IUD),sodium hyalur-onate gel.Group C:large doses of estrogen drugs combined with ball pouch,sodium hyaluronate gel.Group D:large doses of estrogen drugs combined with IUD,sodium hyaluronate gel.Postoperative patients of TCRA were treated by the four therapies respectively for three months.All patients came back for hysteroscopy in one month and three months after operation.Results Following -up period was 6 -12 months.After three months treatment,the total endometrial cavity cure rate was 21.3%(17 /80),the total effective rate was 67.5%(54 /80).The cure rate of group C was 45.0%,which was obviously higher than those of the other three groups,the differences were statistically insig-nificant(group C vs.group A,χ2 =4.29,P <0.05;group C vs.group B,χ2 =6.14,P <0.05;group C vs.group D,χ2 =4.27,P <0.05).After three months treatment,the endometrial thickness were measured during ovulatory period. The thickness of group C was obviously thicker than those of the other three groups,the differences were statistically insignificant(group C vs.group A,t =10.28,P <0.01;group C vs.group B,t =12.80,P <0.01;group C vs.group D,t =5.02,P <0.01).Five months after the operation,in the aspect of menstrual blood volume,the total cure rate was 23.8%(19 /80),the total effective rate was 71.3%(57 /80).And the cure rate of group C was 45.0%,which was obviously higher than those of the other three groups,the differences were statistically insignificant(group C vs. group A,χ2 =4.29,P <0.05;group C vs.group B,χ2 =6.28,P <0.05;group C vs.group D,χ2 =4.27,P <0.05).Conclusion The therapy of large doses of estrogen drugs combined with ball pouch and sodium hyaluronategel can significantly improve the prognosis of serious or moderateIUA,and better than other combined therapies.

Objective:To investigate levels of autophagy in T cells and B cell of patients with systemic lupus erythematosus ( SLE) and its clinical significance.Methods: 68 SLE patients without treatment within 4 weeks were enrolled in this study.We accessed the levels of autophagy in T cells and B cells of 23 healthy controls and 68 patients before and after treatment by flow cytometry,and analyzed their correlations with serum levels of C3 and anti-dsDNA antibodies,SLEDAI score,et al.Results: Before treatment,a significantly increased levels of LC3-Ⅱ was observed in SLE patients than healthy controls, the active group ( SLEDAI score≥10) was significantly higher than the stable group(SLEDAI score<10),and the newly diagnosed group was significantly higher than the recurrent group(all P<0.05).While the levels of LC3-Ⅱ was decreased in B lymphocytes in SLE patients,the active group was significantly lower than stable group,and the active group was significantly lower than the newly diagnosed group(all P<0.05). Correlation analysis found that,a positively correlation was observed for the levels of LC3-Ⅱwith SLEDAI score in T lymphocyte( rs=0.289,P<0.05),and the levels of C3 were positively correlated the levels of LC3-Ⅱ in B lymphocyte(rs=0.371,P<0.01).After treatment for five days, levels of autophagy in T lymphocytes of SLE patients with good prognosis ( SLEDAI score decreased ≥4 ) significantly decreased(P<0.05).Also,three days after treatment,levels of autophagy in B lymphocytes of SLE patients with good prognosis were increased significantly ( P<0.05 ) .However, SLE patients with poor prognosis had no such difference ( P>0.05 ) . Conclusion:Levels of autophagy in T and B lymphocytes of SLE patients are abnormal compared to healthy controls,and these changes are associated with disease activity.Also,these changes are expected to be the indicators of disease activity and potential therapeutic targets in SLE.

OBJECTIVETo investigate the variations of hepatitis C virus (HCV) quasispecies and the changes in their composition in untreated patients with chronic hepatitis C.

METHODSEleven patients chronic hepatitis C without previous specific anti-HCV treatment were tracked for disease progression and blood samples were collected at multiple time points. The major clinical parameters of liver function and viral load were tested. A fragment of HCV hypervariable region 1 (HVR1) was amplified and cloned, and the positive clones were sequenced and subsequently analyzed to determine the composition variation of HCV quasispecies during disease progression in relation to the major clinical parameters.

RESULTSA total of 631 HVR1 sequences were acquired from the positive clones. The evolution of HCV HVR1 quasispecies in untreated chronic hepatitis C patients featured 3 patterns of variation in quasispecies composition, namely stable, fast and slow changes during the natural course of chronic hepatitis C. The genetic distance of the quasispecies was found to inversely correlated with ALT (R=-0.438, P=0.011) and AST level (R=-0.500, P=0.003), and sense mutation rate was also inversely correlated with ALT level (R=-0.387, P=0.026) and AST level (R=-0.410, P=0.018). No significant association was found between HCV load and any clinical or virological parameters.

CONCLUSIONDue to individual differences and immune pressure, HCV quasispecies can present with different patterns of evolution in the natural disease progression of chronic hepatitis C. HCV quasispecies evolution, due to its close correlation with the biochemical parameters, can be used to evaluate the severity and prognosis of chronic hepatitis C.

Objective To analyze the disorder status of calcium-phosphorus metablism in maintenance hemodialysis patients. Methods Serum calcium, serum phosphorus, calcium-phosphorus product and PTH were detected in 70 patients with maintenance hemodialysis ,and compared with the indicators of K/DOQI guidelines. Results There were 36 cases over 50 years age and 34 cases less than 50 years age in 70 cases, and there were no significant differences in serum calcium, serum phosphorus, calcium-phosphorus product and PTH between two groups (P ＞0.05). The longer the dialysis, the more obvious changes of serum phosphorus and PTH levels, and there were significant differences(P ＜0.05). In 70 cases ,46 cases(65. 7%) serum calcium,34 cases(48.6%) serum phosphorus ,40 cases(57. 1%) calcium and phosphorus product,28 cases(40%) PTH met the requirement of K/DOQI guidelines,only 18 cases (25.7%) of all indicators reached the K/DOQI requirements. Conclusion The calcium-phosphorus metablism in most hemodialytic patients still cannot reach the K/DOQI guidelines.