Systemic mastocytosis (SM) with RUNX1-RUNX1T1 positive acute myeloid leukemia (AML) is a rare myeloid tumor with no standard treatment. Two cases of SM patients with RUNX1-RUNX1T1 positive AML treated with sequential avapritinib after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were reported in Henan Cancer Hospital. Mast cell in bone marrow disappeared, C-KIT mutation and RUNX1-RUNX1T1 fusion gene remained negative. Allo-HSCT sequential avapritinib is an effective treatment for SM patients with RUNX1-RUNX1T1 positive AML.

Objective:To investigate the efficacy and safety of avapritinib in the treatment of molecular biologically positive core binding factor-acute myeloid leukemia (CBF-AML) with KIT mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:We retrospectively analyzed the clinical data of six patients with molecular biologically positive CBF-AML with KIT mutation after allo-HSCT, who were treated with avapritinib at Henan Cancer Hospital from December 2021 to March 2023, and evaluated the efficacy and safety of avapritinib.Results:After 1 month of treatment with avapritinib, the transcription level of the fusion gene decreased in six patients, and the transcription level decreased by ≥1 log in five patients. In four patients who received avapritinib for ≥3 months, the fusion gene turned negative, and the median time to turn negative was 2.0 (range: 1.0-3.0) months. Up to the end of follow-up, four patients had no recurrence. The most common adverse reaction of avapritinib was myelosuppression, including neutropenia in two cases, thrombocytopenia in two cases, and anemia in one case. The non-hematological adverse reactions were nausea in two cases, edema in one case, and memory loss in one case, all of which were grades 1-2.Conclusion:Avapritinib was effective for molecular biologically positive CBF-AML patients with KIT mutation after allo-HSCT. The main adverse reaction was myelosuppression, which could generally be tolerated.

Metastasis and resistance are main causes to affect the outcome of the current anticancer therapies. Heat shock protein 90 (Hsp90) as an ATP-dependent molecular chaperone takes important role in the tumor metastasis and resistance. Targeting Hsp90 and downregulating its expression show promising in inhibiting tumor metastasis and resistance. In this study, a redox-responsive dual-drug nanocarrier was constructed for the effective delivery of a commonly used chemotherapeutic drug PTX, and a COA-modified 4-arm PEG polymer (4PSC) was synthesized. COA, an active component in oleanolic acid that exerts strong antitumor activity by downregulating Hsp90 expression, was used as a structural and functional element to endow 4PSC with redox responsiveness and Hsp90 inhibitory activity. Our results showed that 4PSC/PTX nanomicelles efficiently delivered PTX and COA to tumor locations without inducing systemic toxicity. By blocking the Hsp90 signaling pathway, 4PSC significantly enhanced the antitumor effect of PTX, inhibiting tumor proliferation and invasiveness as well as chemotherapy-induced resistance in vitro. Remarkable results were further confirmed in vivo with two preclinical tumor models. These findings demonstrate that the COA-modified 4PSC drug delivery nanosystem provides a potential platform for enhancing the efficacy of chemotherapies.

Objective To investigate the clinical effect of free posterior interosseous artery perforator flap combined with muscle fascia for repairing soft tissue and extensor tendon defect of hand.Methods Fifteen cases of hand skin soft tissue and extensor tendon defect admitted to Ningbo No.6 Hospital from December 2017 to December 2020 were repaired with free posterior interosseous artery perforator flap combined with extensor carpi ulnaris muscle fascia transplantation,and curative effect was observed.Results All flaps survived and patients were followed up for 6-24 months.The texture and thickness of the flap were satisfactory,and the recovery of the finger extension and flexion function were good.The excellent and good rate of hand tendon repair was 66.7%.In three cases with nerve anastomosis,the skin flap sensation recovered to S3.Conclusion The free posterior interosseous artery perforator flap combined with muscle fascia has a good clinical effect in repairing hand skin soft tissue and tendon defect.

Objective:To observe any effect of low-frequency whole body resonant stimulation on the ba-lance and walking ability of hemiplegic stroke survivors.Methods:Sixty-six stroke survivors with hemiplegia were randomly divided into a low-frequency resonance training group, a high-frequency vibration training group and a control group, each of 22. All received routine exercise training at individualized intensities. All three groups underwent five 1-minute cycles of 7Hz, 15Hz or 1Hz stimulation twice a day, five days a week for eight weeks. Before and after the intervention, balance and walking ability were evaluated using the Berg Balance Scale, the timed up and go test and a 10m walking test. Step length, step frequency and step speed were also measured.Results:There were no significant differences among the three groups before the training. Afterward, significant improvement was observed in all of the groups in terms of all of the measurements. The average results of the low-frequency resonance training group were at that point significantly better than the other two groups′ averages, while the high-frequency vibration training group′s results were superior to those of the control group.Conclusion:Resonance training at 7Hz is the most effective in improving the balance and walking ability of stroke survivors with hemiplegia.

Objective To analyze the correlation between function of liver and kidney and blood lipid inde-xes and the prognosis of acute cerebral infarction.Methods 100 patients with acute cerebral infarction were selected.Serum levels of uric acid (UA),serum creatinine (Scr),serum triglyceride (TG),total cholesterol (TC),low density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C),and blood calcium (Ca2+).Fasting blood glucose (FPG),fibrinogen (FIB),D two polymer (D-D),serum homocysteine (Hcy),total bilirubin(TBIL),direct bilirubin (DBIL),and indirect bilirubin (IBIL)UA,Scr,TG,TC,LDL-C, HDL-C,Ca2+,FPG,FIB,D-D,Hcy,TBIL,DBIL and IBIL were measured in all the patients the next morning after admission.According to the CSS score,the patients were divided into mild group (0 -15 points,35 ca-ses),medium group (16~30 pointsminutes,34 cases),heavy group 3(31~45 pointsminutes,31 cases).The NIHSS score difference betweenin the scores of the two patients at admission and three months after the onset of the disease was calculated.The patients were divided into the improved group(score difference >0 points, 58 cases),no change group (score difference = 0,36 cases) aAnd worsening group(score difference < 0 point,6 cases).The levels of serum UA,Scr,TG,TC,LDL-C,HDL-C,Ca2+,FPG,FIB,D-D,Hcy,TBIL, DBIL,IBILof different severity and different prognosis of patients were compared and the relevance were ana-lyzed.Results The levels of UA,Hcy,FIB,DD and,LDL-C were the highest in the heavy group and the low-est in the light group.The levels of Ca2+,TBIL,DBIL and IBIL were the lowest in the heavy group,and the highest in the light group.The differences of above indexes between the three groups were statistically signifi-cant (P<0.05).There were positive correlations between the severity of the disease with serum levels of UA, Hcy,FIB,D-D and LDL-C (P<0.05),and a negatively correlations with serum levels of Ca2+,TBIL,DBIL and IBIL (P<0.05).The levels of UA,Hcy,and LDL-C were the highest in the worsening group and the low-est in the improved group,the levels of TBIL,DBIL and IBIL were the lowest in the worsening group and the highest in the improved group.The differences between the three groups were statistically significant (P<0. 05).The prognosis was positively correlated with serum levels of UA,Hcy and LDL-C (P<0.05),and nega-tively correlated with serum levels of TBIL,DBIL and IBIL(P<0.05).Conclusion The serum levels of UA, Hcy,FIB,D-D,LDL-C,Ca2+,TBIL,DBIL and IBIL were significantly correlated with the severity of acute cer-ebral infarction.The serum levels of UA,Hcy,LDL-C,TBIL,DBIL and IBIL were also correlated with pro-longed prognosis.

Objective: To explore the occurrence, clinical characteristics, diagnosis and treatment of glomerulitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Analysis were carried out based on the clinical data of 6 patients with de novo glomerulitis following allo-HSCT hospitalized in Henan Tumor Hospital from January 2008 to December 2016, and the clinical manifestation, pathology, diagnosis, treatment and outcome were investigated. Results: The occurrence of glomerulitis was 1.26% (6/478). The median time was 447(272-1 495) d after allo-HSCT. Proteinuria and varying degrees of edema were present in all patients. Of the 6 patients, 4 patients with impaired renal function, 3 cases of hypertension, 5 cases of urine occult blood positive, 2 cases of hyperlipidemia. 5 patients underwent acute graft-versus-host disease (GVHD), 4 patients accompanied with chronic GVHD at diagnosis. Kidney pathology showed typical features of minimal change diseases in 1 patient, membranous nephropathy in 4 patients and mesangial proliferative glomerulonephritis in 1 case. Immunohistochemistry of glomerular lesions revealed that the immune complex deposition included IgG in 4 patients, C3 in 3 patients, IgM and C1q in 1 patient. Serum ANA was positive in 2 patients and serum IgG and IgM were in high level in 1 patient, respectively. Only 1 case was effective on glucocorticoid. 5 cases treated by low dose cyclophosphamide combined with mycophenolate mofetil (MMF), 2 cases achieved complete remission, and 3 cases were partial remission. Up to now, 2 cases died with lung infection, and 4 patients survived. Conclusion The predominant pathological type of glomerulitis was membranous nephropathy. Low-dose cyclophosphamide combined with MMF was an effective treatment.

To explore the efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia and granulocytic sarcoma (GS).Clinical outcome including hematopoietic reconstitution,transplant-related complications,survival and relapse were collected and retrospectively analyzed in 9 patients with myeloid leukemia and GS after allo-HSCT.Hematopoiesis reconstitution was achieved in all the 9 recipients.Four cases developed acute graft-versus-host disease (GVHD),and 1 with chronic GVHD.The median follow-up time after transplantation was 10(4-81) months.Only 2 cases survived,the other 7 died of relapse.The median time of relapse after transplantation was 5(3-19) months.Allo-HSCT is relatively effective treatment for patients with myeloid leukemia and GS.Relapse after transplantation remains the major factor of mortality.

Objective To assess the effectiveness of unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of severe aplastic anemia (SAA),and the difference between URD allo-HSCT and matched sibling donor (MSD) allo-HSCT.Methods According to the source of donors,the SAA patients subject to allo-HSCT were divided into MSD allo-HSCT group (MSD group) and URD allo-HSCT group (URD group) from October 2001 to December 2016 in Henan Cancer Hospital.The efficacy and transplantation related complications were compared between two groups.Results There were no statistically significant differences in hematopoietic reconstitution and graft rejection between two groups.The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD was higher in the URD group than in the MSD group (30.76％ vs.8.57％,P =0.026;26.92％ vs.5.71％,P =0.021).However,other transplant-related complications including pulmonary complications and hemorrhagic cystitis,incidence of EBV and CMV reactivation and venous occlusive disease showed no significant difference between two groups.The estimated 5-year over survival was (73.6 ± 8.7) ％ in the MSD group and (72.7 ± 9.5) ％ in the URD group (P =0.878).There was no significant difference in 5-year disease-free survival between two groups (73.6 ± 8.7％ vs.70.3 ± 10.2,P =0.668).Conclusion URD-HSCT is a novel treatment approach and could be considered as first-line therapy in selected patients without MSD.

OBJECTIVETo investigate the characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) and chronic myeloid leukemia (CML).

METHODSThe clinical data of 118 tyrosine kinase inhibitors (TKIs) resistant Ph(+) ALL and CML cases who were detected ABL kinase domain mutation in Affiliated Tumor Hospital of Zhengzhou University from March 2014 to June 2015 were collected. Karyotypes and BCR-ABL fusion gene were analyzed respectively by R-banding, real-time quantitative polymerase chain reaction (PCR). Total RNA was extracted by TRIzol reagent and ABL kinase domain mutation was detected by direct sequencing.

RESULTSIn 23 TKIs resistant Ph(+) ALL and 95 CML cases, the rate of ABL kinase domain mutation was 60.9% (14/23) and 41.1% (39/95), respectively, and the rate of T315I mutation was respectively 34. 8% vs 5.3%, the difference was significant (χ(2)=13.586, P<0.01). The rate of mutations in chronic phase/accelerate phase /blast crisis CML patients was 38.8% (19/49), 47.1% (8/17) and 41.4% (12/29), respectively, and there was no significant difference (χ(2)=0.360, P=0.835). In Ph (+) ALL and CML patients, the median time from the beginning of TKI therapy to appearance of T315I mutation was 10 months and 19 months, the median time from the appearance of T315I to death/deadline was 2 months and 3 months, the median time of persistent hematologic response was 10 months and 16 months and the median time of overall survival (OS) was 13 months and 42 months.

CONCLUSIONT315I mutation was more easily occurred in Ph(+) ALL than CML, but two diseases are similar in the median time from the beginning of TKI therapy to appearance of T315I, the median time of persistent hematologic response and OS.

Acute Disease ; Blast Crisis ; Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; Protein Kinase Inhibitors ; therapeutic use