Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10 8/kg, and the number of CD34 + cells was 3.29 (2.53-6.10) ×10 6/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022.Methods:A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed.Results:① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype ( P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points ( P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ ( P<0.001, HR=5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% –80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively ( P=0.690) . Conclusion:Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient’s OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.

Objective:To investigate the risk factors for concomitant cardiac autonomic neuropathy in diabetic patients and to develop a Nomogram prediction model.Methods:One hundred and fifty-eight diabetic patients admitted to in Southern Hospital Zengcheng Branch from March 2019 to March 2021 were selected. Patients with normal heart rate variability were the diabetic group, and patients with abnormal heart rate variability were the group with diabetes mellitus complicated by cardiac autonomic neuropathy. Logistic regression analysis was used to analyze the risk factors of cardiac autonomic neuropathy. Nomogram models were developed and model performance was evaluated. Decision curve analysis (DCA) was used to assess the net clinical benefit of the Nomogram model.Results:Comparison of general data showed that fasting blood glucose, tumour necrosis factor-α (TNF-α), glomerular filtration rate (eGER), uric acid, C-reactive protein (CRP), interleukin-6 (IL-6), free fatty acids (FFA), standard deviation of sinus heart beat RR interval (SDNN), and duration of diabetes compared to the diabetic group had statistically significant ( P<0.05); the results of the subject work characteristics (ROC) curve analysis showed that the best cut-off values for fasting glucose, TNF-α, eGFR, uric acid, CRP, IL-6, FFA, SDNN and duration of diabetes were >7.53 mmol/L, >98.45 ng/L, ≤94.79 ml/(min·1.73 m 2), > 87.3 μmol/L, >6.22 μmol/L, >37.84 ng/L, >839.19 μmol/L, ≤ 95.88 ms, >9 years; multi-factorial Logistic regression analysis showed that fasting glucose (>7.53 mmol/L), TNF-α (>98.45 ng/L), CRP (>6.22 μmol/L), IL-6 (>37.84 ng/L), FFA (>839.19 μmol/L), SDNN (≤95.88 ms), and duration of diabetes (>9 years) were risk factors for the development of cardiac autonomic neuropathy in diabetic patients; internal validation showed that the Nomogram model predicted a C-index of 0.706 (95% CI 0.668 - 0.751) for the risk of cardiac autonomic neuropathy. The DCA results showed that the Nomogram model predicted a risk threshold of >0.25 for the development of cardiac autonomic neuropathy and that the Nomogram model provided a net clinical benefit. Conclusions:There are many risk factors for cardiac autonomic neuropathy, and the nomogram model based on risk factors in this study has good predictive power and may provide a reference for clinical screening of high-risk patients and further improvement of treatment planning.

Objective:TP53-abnormal MDS/acute myeloid leukemia (AML) patients’ allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment’s effectiveness and influencing factors should be studied.Methods:42 patients with TP53 gene status change MDS/AML who underwent allo-HSCT from 2014.8.1 to 2021.7.31 at the Hematology Hospital of the Chinese Academy of Medical Sciences were the subject of a retrospective analysis. The 42 patients were divided into three groups: the TP53 deletion group (group A) , TP53 mono-alle mutation group (group B) , and TP53 multi-hit group (group C) . The differences in clinical features and prognostic factors after transplantation were analyzed.Results:There were 42 MDS/AML patients, including 21 patients with MDS, and 21 patients with AML. The median follow-up period was 34.0 (7.5-75.0) months and the median patient age at the time of transplantation was 41.5 (18-63) years old. The total OS was 66.3% (95% CI 53.4%-82.4%) in 3 years after transplantation, and EFS was 61.0% (95% CI 47.7%-78.0%) in 3 years. For 3 years after receiving hematopoietic stem cell transplantation, there were no statistically significant differences in 3-year OS and EFS in groups A, B, and C ( P≥0.05) . The 3 years OS was 82.5% (95% CI 63.1%-100.0%) in group A, 60.6% (95% CI 43.5%-84.4%) in group B, and 57.1% (95% CI 30.1%-100.0%) in group C. Univariate analysis revealed that the number of co-mutant genes, pre-HSCT treatment, and disease type did not affect prognosis, while age, karyotype, co-mutation, positive blast cell before transplantation, and positive blast cell after transplantation were common prognostic factors for OS and EFS ( P<0.1) . MRD levels before transplantation were found to be independent risk factors for OS ( P=0.037, HR=33.40, 95% CI 1.24-901.17) in a multivariate analysis. Conclusion:Patients with MDS/AML who have TP53 mutations can benefit from allo-HSCT, but patients with complex karyotypes have a worse prognosis. Meanwhile, the final flow cytometry (FCM) monitoring blast cell test before HSCT has a certain guiding significance for prognostic assessment.

Objective: To explore the effect of miniscrew-assisted rapid palatal expansion (MARPE) on mandible position in the treatment of adult skeletal Class Ⅰ malocclusion with maxillary transverse deficiency. Methods: In this retrospective study, 20 cases of adult skeletal Class Ⅰ malocclusion with maxillary transverse deficiency treated with MARPE in our hospital from July 2019 to March 2022 were selected as research objects. CBCT data of three time points before treatment (T0), immediately after expansion (T1) and six months after retention (T2) were collected. The head position was standardized and calibrated by Dolphin software, and then mandible landmarks (left and right Condylion, left and right Gonion, Menton) were positioned. The linear distance changes of each landmark relative to the reference plane of coronal plane, axial plane and sagittal plane were measured, which represented the sagittal, vertical and horizontal displacement of mandible respectively. Repeated measurement ANOVA and LSD multiple comparison were used to evaluate the position change of each landmark. Results : The Menton and right Gonion rotated clockwise at T1, and relapsed to the initial position at T2. No lateral displacement of Menton was found. Conclusion When MARPE is used to treat skeletal Class Ⅰ malocclusion with maxillary transverse deficiency, it causes a transient clockwise rotation of the mandiblar. The mandible does not show sagittal, vertical and horizontal position changes in long-term evaluation.

【Objective】 To evaluate the application value of nucleic acid testing (NAT) by studying the NAT-yield of syphilis screening reactive blood from five blood centers. 【Methods】 The blood samples and demographic information of syphilis screening positive donors were collected from five domestic blood centers, i. e. Chongqing, Guangxi, Luoyang, Liuzhou, Mianyang and Urumqi. The treponema pallidum particle agglutination (TPPA) and the established SYBR Green qPCR method were used to analyze the difference between the results of NAT and the other two test results. 【Results】 Among 1 679 reactive blood samples for syphilis screening, 819 were confirmed positive by TPPA, accounting for 49%, with the false positive rate exceeded 50%. As to NAT results, the NAT-yield of syphilis screening reactive samples and confirmed positive samples was the same (both 2.20%); the NAT-yield of TPPA-positive and TPPA-negative samples were 2.20% and 2.74%, respectively. 【Conclusion】 Primary syphilis screening by ELISA has high sensitivity, but also presents high false positive rate. Although TPPA confirmatory test has strong specificity, it cannot reflect the existence of T. pallidum. Therefore, NAT may be used as a supplementary test for syphilis screening so as to more effectively ensure the safety of blood transfusion and blood supply.

Objegtive:To investigate the efficacy and safety of preemptive/salvage therapy with venetoclax (VEN) in patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Retrospective analysis the clinical data of 25 patients with minimal residual disease (MRD) positive or morphological recurrence after allo-HSCT treated with VEN in the hematological Hospital of Chinese Academy of Medical Sciences from 2021.2 to 2021.11, there were 15 MRD positive patients (preemptive treatment group) and 10 morphological recurrence patients (salvage treatment group) . The dose of VEN in both groups was 400 mg/d, which was reduced to 100 mg/d when combined with azole antifungal drugs.Results:①In the preemptive group, there were 7 males and 8 females, with a median age of 32 (18-52) years; There were 13 cases of acute myeloid leukemia (AML) , 1 case of acute lymphoblastic leukemia (ALL) and 1 case of primary myelofibrosis (PMF) ; the median time from MRD positive to the application of VEN was 2.5 (0-12.5) months. The median course of treatment was 2 (1-4) . On the 7th day of the first course of treatment, the median concentration of VEN was 1945 (688-5383) μg/L. After one course of VEN treatment, MRD in 8 patients turned negative (major responses) , MRD in 4 patients decreased by 50% compared with that before treatment, 3 cases were ineffective, and the overall response rate (ORR) was 80% (12/15) . On the 7th day of treatment, 3 of the 9 patients with VEN blood concentration <1 000 μg/L or >3 000 μg/L turned negative for MRD (33.3%) , and 5 of the 6 patients with VEN blood concentration between 1000 and 3000 μg/L turned negative for MRD (83.3%) . Grade 3/4 neutropenia occurred in 5 patients (33%) and grade 3/4 thrombocytopenia occurred in 5 patients (33%) , there were no new cases of severe infection and death. ②In the salvage group, there were 7 males and 3 females, with a median age of 44 (28-59) years; there were 6 cases of AML, 2 cases of ALL, 1 case of atypical chronic myeloid leukemia (aCML) , 1 case of refractory hemopenia with multiline dysplasia (MDS-RCMD) ; the median time from relapse to application of VEN was 0 (0-1) months. The median treatment was 1 (1-2) course. The median concentration of VEN on the 7th day of the first course of treatment was 2 419 (1 200-6 155) μg/L. After one course of VEN treatment, 3 cases achieved complete remission (CR) (major responses) and 3 cases achieved partial remission (PR) , 4 cases were ineffective and the ORR was 60% (6/10) . On the 7th day of treatment, 1 of the 4 patients with VEN blood concentration >3 000 μg/L achieved CR (25%) , and 2 of the 6 patients with VEN blood concentration between 1 000 and 3 000 μg/L achieved CR (33.3%) . Grade 3/4 neutropenia and grade 3/4 thrombocytopenia occurred in 10 patients (100%) . One patient died of severe pulmonary infection. ③The median follow-up was 4.5 (1-8.5) months. The overall survival rate (OS) of the preemptive group and the salvage group were (70.2±12.7) % and (50.0± 15.8) %, respectively ( χ2=1.873, P=0.171) . The OS of patients with and without primary response to one course of VEN were (90.9±8.7) % and (36.2±14.7) % respectively ( χ2=6.843, P=0.009) . Three patients with TP53 mutation achieved the major responses after VEN treatment. Conclusion:Preemptive/salvage therapy with VEN after allo-HSCT in patients with hematological malignancies is effective and well tolerated, monitoring the concentration of VEN is expected to improve the curative effect. The prognosis of patients who fail to reach the major responses after one course of preemptive/salvage treatment with VEN is poor, so they need to switch to other treatment schemes as soon as possible.

Objective:To analyze the characteristics of the molecular transmission network of newly-diagnosed human immunodeficiency virus type 1 (HIV-1) infected individuals in Shaoxing City, Zhejiang Province, and to provide evidence for epidemic trend and prevention.Methods:The plasma samples from 423 antiretroviral-naive HIV-1/acquired immunodeficiency syndrome patients from August 2018 to December 2019 were collected, and the pol gene fragments of HIV-1 from 375 samples were amplified by reverse transcription polymerase chain reaction (PCR) and nested PCR. The phylogenetic tree was constructed to analyze the molecular transmission network for subtypes and different gene distances by MEGA 6.0 software, HyPhy software and Cytoscape 3.7.2. Mutations on drug resistance was analyzed by online software tool of the HIV drug resistance database of Stanford University. Results:Eight subtypes were found in the 375 samples. Circulating recombinant form (CRF)07_BC(215/375, 57.33%) and CRF01_AE(103/375, 27.47%) were the major subtypes, followed by CRF85_BC, CRF55_01B, B, C, and CRF01_AE/B subtypes. One hundred and ninety-four individuals (51.73%) were connected to the transmission network at 1.50% genetic distance with 24 clusters. One hundred and twenty-nine individuals (34.40%) were connected to the transmission network at 0.75% genetic distance with 30 clusters, and 35 elderly patients were clustered in CL1.Forty-two cases had surveillance drug resistance mutation (SDRM), the prevalence of transmitted drug resistance was 11.20%(42/375). Thirty-eight cases had the drug mutations to non-nucleoside reverse transcriptase inhibitor, including K103 N(32/375, 8.53%), K103 S(4/375, 1.07%), Y188 L(1/375, 0.27%) and G190 A(1/375, 0.27%); four cases had the mutations to protease inhibitor, including M46 I(3/375, 0.80%) and V82 A(1/375, 0.27%). The cluster C2 sequences carried a high proportion of resistant mutations (94.29%, 33/35). Conclusions:HIV-1 subtypes in Shaoxing City are diverse and the CRF07_BC subtype spreads rapidly. The elderly patients with drug resistance genes in cluster CL1 at 0.75% gene distance need to be intervened immediately to prevent the drug resistance virus spread.

OBJECTIVE：To optim ize the ultrafiltration technology of enzymatic hydrolysate from Eucommia ulmoides peel. METHODS：The single factor test was adopted to investigate the effects of molecular weight of ultrafiltration membrane ，liquid temperature，operating pressure ，operating frequency ，membrane filtration time ，liquid concentration and pH on transfer rates of aucubin，geniposide and chlorogenic acid as well as solid removal rate in enzymatic hydrolysate from E. ulmoides peel. Setting the molecular cut off of fixed ultrafiltration membrane of 100 000，liquid concentration of 7 g/L，and pH value of 7，the ultrafiltration technology was optimized by Box-Behnken design response-surface methodology and validated with liquid temperature ，operating pressure，operating frequency and membrane passing time as factors ，using comprehensive scores calculated from transfer rates of aucubin，geniposide and chlorogenic acid as well as solid removal rate as indexes. RESULTS ：The optimal ultrafiltration technology of enzymatic hydrolysate from E. ulmoides peel was as follows as liquid temperature of 35 ℃，operating pressure of 0.5 MPa，operating frequency of 35 Hz and membrane passing time of 42 min. Results of validation tests showed that the comprehensive scores of the transfer rates of aucubin ，geniposide and chlorogenic acid as well as solid removal rate in enzymatic hydrolysate from E. ulmoides peel was 78.06％（RSD＝1.43％，n＝3），and its relative error with the predicted value （77.18％） was 1.14％. CONCLUSIONS ：The optimized ultrafiltration technology is stable and reliable ，and can be used for the ultrafiltration purification of enzymatic hydrolysate from E. ulmoides peel.

Objective:To evaluate the outcomes and prognostic factors of adults with acute myeloid leukemia with myelodysplastic-related changes (AML-MRC) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) . The genetic mutation lineage of patients with AML-MRC and the molecular mutation affecting the transplantation prognosis was discussed.Methods:The clinical data of 75 patients with AML-MRC who underwent allo-HACT from 2006 to 2020 were retrospectively analyzed for clinical characteristics, survival, relapse-related indicators, and risk factors affecting transplantation prognosis. Additionally, the clinical characteristics and prognosis of multilineage dysplasia (M) group, history of myelodysplastic syndrome (MDS) or myelodysplastic syndrome/myelodysplastic proliferative tumor (MDS/MPN) (H) group, and MDS related cytogenetic abnormalities (C) group were compared. The bone marrow of 43 patients underwent targeting second-generation sequencing (137 genes) .Results:①There were 41 males and 34 females with a median age of 41 (18-56) years, a median follow-up time of 35 (95% CI 30-49) months, and a median survival time (OS) of 78 (95% CI 23-) months. Three-year OS and event-free survival (EFS) were 57.1% (95% CI 45.6%-71.4%) and 52.0% (95% CI 40.8%-66.1%) . Also, the three-year cumulative recurrence rate (CIR) and transplant-related mortality rate (TRM) were 26.8% (95% CI 16.6%-30.0%) and 22.7% (95% CI 13.2%-33.8%) , respectively. Furthermore, multivariate analysis revealed that pre-transplant non-CR1 status was an independent risk factor for OS and EFS. Other independent risk factors for OS included abnormal karyotype of -5/5q- chromosome and the absence of chronic graft-versus-host disease (cGVHD) after transplantation. ②Among the 75 patients, 59 (78.7%) were in group H, 20 had received demethylation drugs before turning to AML and nine cases (12.0%) in group C and seven cases (9.3%) in group M. There was no significant difference in the three-year OS and EFS among the three groups[group M vs H vs C: OS: 71.4% (95% CI 44.7%-100.0%) vs 55.0% (95% CI 41.8%-72.5%) vs 55.6% (95% CI 31.0%-99.7%) , P=0.700; EFS: 71.4% (95% CI 44.7%-100.0%) vs 46.5% (95% CI 34.0%-63.8%) vs 55.6% (95% CI 31.0%-99.7%) , P=0.600]. Compared with primary and secondary AML-MRC, there was no statistically significant difference in the three-year OS and EFS[61.9% (95% CI 41.9%-91.4%) vs 55.0% (95% CI 41.8%-72.5%) , P=0.600; 61.9% (95% CI 41.9%-91.4%) vs 46.5% (95% CI 34.0%-63.8%) , P=0.400]. Furthermore, there was no significant difference in the time to AML between patients who received demethylation treatment before (20 cases) and those who did not (39 cases) [195 (16-937) d vs 162 (9-3167) d, P=0.804]. Moreover, there were no statistically significant differences in the three-year OS and EFS between the two groups ( P=0.400, P=0.700) . ③ NGS test was performed on bone marrow samples of 43 patients (57.3%) , and 73 mutation types were found. Additionally, U2AF1 had the highest mutation incidence (11 cases, 25.6%) , and more than 10% were found: RUNX1 (ten cases, 23.3%) , NRAS (ten cases, 23.3%) , ASXL1 (six cases, 14.0%) , PTPN11 (five cases, 11.6%) , TET2 (five cases, 11.6%) . Univariate analysis showed U2AF1[ P=0.875, HR=1.110 (95% CI 0.295-4.195) ], RUNX1[ P=0.685, HR=0.728 (95% CI 0.157-3.375) ], NRAS[ P=0.919, HR=0.923 (95% CI 0.196-4.334) ] mutation did not affect OS. Conclusion:Chromosome abnormality of -5/5q-, cGVHD, and non-CR1 status before transplantation were independent risk factors for OS in patients with allo-HSCT and AML-MRC. Additionally, the MHC subgroup classification was not a factor affecting the prognosis of transplantation. Treatment with demethylated drugs may not delay MDS turning to AML and prolong the OS after transplantation.