Objective:The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored.Methods:A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored.Results:Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS ( P<0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS ( P=0.001, HR=6.981, 95% CI 2.186-22.300; P=0.010, HR=6.719, 95% CI 1.572-28.711; P=0.026, HR=3.386, 95% CI 1.158-9.901; P=0.006, HR=0.151, 95% CI 0.039-0.581) . Conclusion:For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.

Objective:To explore the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML) patients with BCR::ABL1 fusion.Methods:The clinical data of seven AML patients with BCR::ABL1 fusion from November 2012 to January 2022 were retrospectively analyzed, and their survival status was followed up.Results:The median age of patients at the time of diagnosis was 35 years. Four cases (57.1%) were diagnosed with high leukocyte counts. All cases were assayed as BCR::ABL1 positive and accompanied by four types of gene mutations (NPM1, RUNX1, ASXL1, PHF6) . Seven patients received tyrosine kinase inhibitor (TKI) combined with induction chemotherapy and bridged to allo-HSCT, and six patients received maintenance therapy with TKI. Before allo-HSCT, six patients achieved complete remission, and four patients achieved complete molecular remission (CMR) . After allo-HSCT, the three remaining cases also achieved CMR. All patients were in remission post-allo-HSCT. One case died of infection, and the remaining cases survived without relapse. The 3-year cumulative overall survival rate was (80.0±17.9) %.Conclusions:TKI combined with traditional chemotherapy could achieve a high response rate in AML patients with BCR::ABL1 fusion. In addition, allo-HSCT could enhance the molecular response rate. Maintenance therapy post-HSCT with TKI could improve prognosis.

Objective:To form the expert consensus on screening and evaluation of dysphagia with oral cancer patients (abbreviated as Consensus) , so as to standardize the relevant contents of screening and evaluation of dysphagia in the whole cycle of oral cancer. Methods:By referring to domestic and foreign literature related to dysphagia, combining with the specialty characteristics of oral cancer and the clinical experience of experts, a preliminary consensus was formed through in-depth interviews with experts. A total of 21 experts were selected for three rounds of expert letter consultation and expert meeting, the corresponding items were sorted out, analyzed and modified based on expert opinions, and the Consensus was finally formed. Results:The effective recovery rates of the three rounds of correspondence were 100.00% (21/21) , the expert authority coefficient was 0.91, the variation coefficient of each item was 0.04-0.20, and Kendall's harmony coefficient was 0.05 ( P<0.05) . The final consensus included four aspects, such as the effect of oral cancer on swallowing, the clinical manifestations of dysphagia, the basic procedures of screening and evaluation and the prevention and treatment of complications during evaluation. Conclusions:This Consensus is scientific and practical, which can provide clinical guidance for the screening and evaluation of dysphagia in the whole cycle of oral cancer.

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ²=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ²=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ²=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4⁺， and CD4⁺/CD8⁺ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19^-， HLA/DR⁺， and CD25⁺ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4⁺， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.

[摘 要] 目的：探讨超微氧化铁纳米粒子（ultrasmall iron oxide nanoparticle，USIONP）对人肝细胞癌HepG2细胞迁移和侵袭的影响及其可能的机制。方法：采用粒径分析仪和透射电镜分别分析USIONP的水合粒径和核心粒径，Zeta电位和胶体稳定性实验分析USIONP的分散性及其稳定性以鉴定USIONP的成功制备；用不同质量浓度USIONP（0、50、100、200 μg/ml）或200 μg/ml USIONP+5 mmol/L 3-MA（自噬抑制剂）联合处理HepG2细胞，CCK-8法检测HepG2细胞的增殖活力，Transwell法检测细胞的迁移和侵袭能力，WB实验检测自噬标志物Beclin1、LC3、p62的表达，2’,7’-二氯二氢荧光素二醋酸（DCFH-DA）法测定细胞内活性氧（ROS）水平，铁离子比色法检测细胞内铁离子水平。结果：USIONP的平均水合粒径为（37.86±12.90） nm、核心粒径约10 nm，Zeta电位为–23.8 mV，有良好的水溶分散性，证实了USIONP的成功制备。随USIONP质量浓度升高和处理时间延长，HepG2细胞的增殖活力明显降低（均P<0.05）；与对照组相比，200 μg/ml USIONP处理HepG2细胞24 h后，迁移、侵袭细胞数量均显著减少（均P<0.05），而3-MA能够部分抵消上述影响（均P<0.05）。与对照组相比，100、200 μg/ml USIONP处理组的HepG2细胞中Beclin1和LC3Ⅱ蛋白相对表达水平均显著升高（均P<0.05），而p62蛋白表达水平下降（均P<0.05）；200 μg/ml USIONP可显著提高细胞内ROS水平与铁离子水平，而加入3-MA可阻断其作用（均P<0.05）。结论：USIONP能促进HepG2细胞发生自噬，而自噬通路激活后降解USIONP释放铁离子和导致细胞ROS水平升高，从而抑制HepG2细胞的迁移和侵袭。

Objective:To evaluate the prognostic significance of neoadjuvant rectal (NAR) score and downstaging depth score (DDS) after neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC).Methods:Retrospective analysis was performed for 200 patients with LARC (T 3-T 4 and/or N 1-N 2, M 0), who were initially treated in the Cancer Hospital of Chinese Academy of Medical Sciences from 2015 to 2018. All patients had baseline MRI data and received preoperative nCRT and radical resection. All patients received preoperative radiotherapy with a dose of 45-50Gy combined with concurrent capecitabine. The effect of NAR and DDS scores on clinical prognosis was statistically compared. The 3-year disease-free survival (DFS) was calculated using the Kaplan- Meier method and compared by the log- rank test. Cox proportional hazards model was used to perform multivariate survival analysis. The predictive performance for 3-year DFS was calculated using the receiver operating characteristic (ROC) curve. Results:The median follow-up time was 30.5(10.6-54.0) months. In terms of DDS, the 3-year DFS rate was 56.4% in the DDS ≤0 group, significantly lower than 83.0% in the DDS >0 group ( P=0.002). In terms of NAR score, the 3-year DFS rates were 90.1%, 73.8% and 53.6% in NAR score ≤8, 8-16 and>16 groups, respectively ( P<0.001). In the whole cohort, the area under the ROC curve (AUC) of DDS and NAR scores for predicting 3-year DFS were 0.683 and 0.756( P=0.037). In yp0-I stage patients ( n=72), the AUC of DDS and NAR scores for predicting 3-year DFS were 0.762 and 0.569( P=0.032). Conclusions:High DDS and low NAR scores after nCRT indicate good prognosis for patients with LARC. NAR score yields better accuracy than DDS in predicting clinical prognosis, but DDS is significantly better than NAR score in yp0-I stage population.

Objective:To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) model of" neoadjuvant chemoradiotherapy plus consolidation neoadjuvant chemotherapy (CNCT) followed by surgery" for locally advanced gastric cancer.Methods:From 2018 to 2020, 28 patients clinically diagnosed with locally advanced gastric adenocarcinoma or Siewert Ⅱ/Ⅲ adenocarcinoma gastroesophageal junction cancer were prospectively enrolled. The neoadjuvant chemoradiotherapy (NCRT) was delivered with a total dose of 45 Gy, 1.8 Gy/f. Concurrent chemotherapy was S-1 at a dose of 40-60 mg twice daily. Then, patients received four to six cycles of CNCT of SOX regimen at three weeks after neoadjuvant chemoradiotherapy. D 2 lymphadenectomy was performed at 4-6 weeks after CNCT. Results:A total of 28 patients completed the whole therapy. Grade 3 or above adverse events occurred in 3 cases (11%) during CCRT, including thrombocytopenia, leukopenia and anorexia; 2 cases (7%) developed leukopenia and 3 cases (11%) of thrombocytopenia during CNCT. Twenty patients (71%) completed the surgery. The proportion of patients with pathological complete remission (pCR) was 50%. Three patients experienced surgical complications including anastomotic leak, anastomotic stenosis and intra-abdominal sepsis. All were recovered after symptomatic treatment.Conclusion:Interim analysis results demonstrate that TNT can yield significant down-staging for patients with locally advanced gastric cancer, which causes tolerable adverse events and postoperative complications.

Objective:To investigate the relationship between MRI parameters and clinical prognosis before and after chemoradiotherapy in patients with locally advanced rectal cancer.Methods:Clinical and follow-up data of 96 patients with locally advanced rectal cancer who were initially treated in the Cancer Hospital of Chinese Academy of Medical Sciences from 2015 to 2017 were retrospectively analyzed. All patients received preoperative chemoradiotherapy, followed by delayed radical surgery at 6-13 weeks after radiotherapy. MRI assessment was performed twice around radiotherapy which were within 4 weeks before the treatment and 4-8 weeks after it. Correlation analysis was utilized to determine the association between MRI assessment and 3-year disease-free survival (DFS).Results:Of the all patients, 80 (83%) had T 3 stage, 16(17%) had T 4 stage, 14 (15%) had N 0 stage, and 82 (86%) had N 1-2 stage. Among them, 69(72%) and 58(60%) patients were positive for MRF and EMVI. The median dose of radiotherapy was 50 Gy, and all patients were sensitized by simultaneous capecitabine. After chemoradiotherapy, T-downstage rate of the whole group was 24%, and 50% for the N-downstage rate. The MRF-and EMVI-positive rates were significantly decreased to 37% and 27% after chemoradiotherapy (both P<0.001). Univariate and multivariate analyses showed that N staging and EMVI status change were significantly correlated with the 3-year DFS. Conclusion:MRI after concurrent chemoradiotherapy reveals that positive EMVI throughout the treatment and N 1-N 2 staing are poor prognostic factors of DFS, suggesting the need for improving the treatment.

Objective: To investigate the effects of donor-specific HLA antibodies(DSA) for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT) and the feasible treatment for DSA. Methods: HLA antibodies were examined using the Luminex-based single Ag assay for 92 patients who were going on haplo-SCT and the correlations of graft failure and DSA among the patients who had finished SCT were analyzed. Results: Of the total 92 patients who were going on haplo-HSCT, sixteen (17.4%) patients were HLA Ab-positive, including six (6.5%) patients with antibodies corresponding to donor HLA Ags (DSA-positive). Among the patients who had finished the haplo-HSCT with conventional myeloablative conditioning regimen, the engraftment rate was significantly higher in DSA (-) patients than that in DSA (+) patients [92.3% (24/26) vs 25.0%(1/4), χ²=8.433, P=0.004] and DSA was the only factor relevant with graft failure in multiple-factor analysis [OR=12.0(95% CI 1.39-103.5), P=0.024]. Strategies to decrease antibody levels were taken for 4 patients, two were their first transplantations, and the other two patients were their second haplo-HSCT. Three of the four patients were HLA-I-DSA positive and had gained donor engraftment by means of donor platelet transfusions to decreased the level of DSA, the fourth patient with both HLA-I and HLA-II DSA also gained engraftment with the treatments of TBI, rituximab and donor platelet transfusion. Conclusion DSA is one of the key factors of graft failure in haplo-HSCT. Donors should be selected on the basis of an evaluation of HLA antibodies before transplantation. If haplo-HSCT from donors with DSA must be performed, then recipients should be treated for DSA to improve the chances of successful engraftment.

Objective To investigate the pattern of nodal recurrence after curative resection in adenocarcinoma of the gastroesophageal junction ( AGE ) , and to provide a basis for delineation of the radiation range in the high-risk lymphatic drainage area.Methods A retrospective analysis was performed in 78 patients with locally advanced AGE who were newly treated in our hospital from January 2009 to December 2013 and had complete clinical data.All patients received curative resection and were pathologically diagnosed with stage T3/T4 or N (+) AGE.Those patients were also diagnosed with SiewertⅡor Ⅲ AGE by endoscopy, upper gastroenterography, macroscopic examination during operation, and pathological specimens.None of the patients received preoperative or postoperative radiotherapy.All patients were diagnosed by imaging with postoperative nodal recurrence.The computed tomography images of those
patients were accessible and had all the recurrence sites clearly and fully displayed.Results The median time to recurrence was 10 months ( 1-48 months) , and 90%of the recurrence occurred within 2 years after surgery.The lymph nodes with the highest risk of recurrence were No.16b1( 39%) , No.16a2( 37%) , No.9 (30%), and No.11p (26%), respectively.There was no significant difference in the recurrence rate within each lymphatic drainage area between patients with SiewertⅡandⅢAGE ( P=0.090-1.000) .The lymph nodes with the most frequent recurrence were No.16b1, No.16a2, No.9, No.16b2, No.11p, and No.7 in patients with stage N3 AGE and No.11p, No.16b1, No.16a2, No.9, No.8, and No.7 in patients with stage non-N3 AGE.Patients with stage N3 AGE had a significantly higher recurrence rate in the para-aortic regions (No.16a2-b2) than those with stage non-N3 AGE (67%vs.33%, P=0.004, OR=4.00, 95% CI=1.54-10.37) .Conclusions The lymph nodes with the highest risk of recurrence are located in the celiac artery, proximal splenic artery, and retroperitoneal areas ( No.16a2 and No.16b1) in patients with SiewertⅡorⅢlocally advanced AEG.Moreover, patients with stage N3 AGE have a higher risk of retroperitoneal recurrence.The above areas should be involved in target volume delineation for postoperative radiotherapy.