Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:This study aims to evaluate the safety and effectiveness of gilteritinib (Gilt) -based combination therapy bridging allo-HSCT for FLT3-ITD + R/R AML. Additionally, it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT. Methods:The clinical data of 26 patients with FLT3-ITD + R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed. The analysis included an assessment of the composite complete remission rate (CRc), overall survival (OS) time, disease-free survival (DFS) time, and adverse events experienced by all enrolled patients. Results:A total of 26 patients with FLT3-ITD + R/R AML were enrolled, including 14 men and 12 women with a median age of 38 (18-65) years. A total of 18 cases were refractory, and eight cases were relapsed. The curative effect evaluation conducted between 14 and 21 days showed that the complete remission (CR) rate was 26.9% (7/26), the CR with hematology incomplete recovery was 57.7% (15/26), and the partial response (PR) rate was 7.7% (2/26). The CRc was 84.6% (22/26), and the minimal residual disease (MRD) negativity rate was 65.4%. The 12 month cumulative OS rate for all patients was 79.0%, and the 24 month cumulative OS rate was 72.0%. The median OS time was not determined. The median follow-up time was 16.0 months. Among the patients who responded to treatment, the 12 month cumulative DFS rate was 78.0%, and the 24 month cumulative DFS rate was 71.0%. The median DFS time was not determined. Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT (3.3 months, 95% CI 2.2-4.3 months, P=0.005). The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined, but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment ( P=0.019). The FLT3-ITD mutation clearance rate in this study was 38.5%, and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance (15.0 months; P=0.018). The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia (76.9%), neutropenia (76.9%), febrile neutropenia (61.5%), thrombocytopenia (69.2%), and anemia (57.7%). One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment, but his condition improved after treatment. Conclusion:The Gilt-based combination therapy is highly effective in treating FLT3-ITD + R/R AML. It demonstrates a high CRc, MRD negativity rate, and rapid onset, leading to a significant improvement in patients' survival. Furthermore, the clearance rate of FLT3-ITD mutation is notably high. Additionally, implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients' survival. Closely monitoring and managing any adverse event that may occur during treatment are crucial.

A retrospective analysis of the clinical data of seven acute B-lymphoblastic leukemia (B-ALL) patients with TCF3-HLF fusion gene-positive admitted to the First Affiliated Hospital of Soochow University from June 2017 to August 2022 was conducted to summarize their clinical features and prognoses. The seven B-ALL patients comprised four males and three females, with a median age of 18 (11-33) years. Five patients tested positive for CD33 expression, and four patients had a normal karyotype. Two patients had hypercalcemia at the initial diagnosis, and one patient developed hypercalcemia at relapse. Six patients presented with coagulation dysfunction at diagnosis. After induction chemotherapy, five out of seven patients achieved complete remission, of which four subsequently relapsed. Two patients did not achieve remission even after two rounds of induction chemotherapy, with one achieving complete remission after treatment with blinatumomab immunotherapy. Three patients underwent chimeric antigen receptor T cell therapy, whereas three patients subsequently underwent hematopoietic stem cell transplantation. Five patients died, while two patients survived with sustained complete remission. TCF3-HLF-positive B-ALL is rare and has a high relapse rate and poor prognosis.

Objective:To investigate the optimal angle of bedhead elevation during logrolling of patients with severe stroke supported by continuous enteral nutrition via gastric tube administration, and to provide a basis for safe infusion of enteral nutrition in clinical practice.Methods:This study was a prospective study, and the repeated measurement method was used. A total of 154 patients with severe stroke who were admitted to the Neurology Intensive Care Unit of the the 960th Hospital of the Joint Logistic Support Force of the Chinese People′s Liberation Army and treated with continuous enteral nutrition support from January to October 2023 were selected as the study participants by convenience sampling method. The times and duration of cardia reflux in 5 min were observed under ultrasound when the bedhead elevation angle during logrolling of the study participants was 30°, 20°, 10°, and 0°, respectively, and the incidence of reflux and aspiration during the observation period were recorded.Results:A total of 148 patients were eventually included. Among them, 81 were males and 67 were females, aged 38-80 (65.79 ± 10.96) years. There were no significant differences in the incidence of reflux [18.24% (27/148) vs. 12.16% (18/148)] and aspiration [4.05% (6/148) vs. 1.35% (2/148)] when the angle of bedhead elevation during logrolling of patients with continuous enteral nutrition via gastric tube administration was 10° and 20° (all P>0.05). Nevertheless, compared with the incidence of reflux [37.16% (55/148)] and aspiration [(10.81% (16/148)] at the bedhead elevation angle of 0°, those measured at 10° or 20° were significantly different ( χ2 values were 4.91-24.89, all P<0.05). Conclusions:For patients with severe stroke supported by continuous enteral nutrition, bedhead elevation angle of 10° can not only prevent aspiration caused by gastric reflux, but also conform to the labor-saving principle during logrolling, which is the recommended angle of logrolling for patients with severe neurological diseases supported by continuous enteral nutrition.

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

Objective:To explore the clinical application value of rapid next-generation sequencing (NGS) strategy based on targeted amplicon sequencing in the diagnosis of myeloid neoplasms.Methods:In this observational study, both rapid NGS and conventional NGS on the bone marrow or peripheral blood samples of 682 patients were prospectively performed from February 2021 to August 2022 in First Affiliated Hospital of Soochow University. The sequencing results were analyzed using the local Ion Reporter software and our lab′s self-built bioinformatics platform, respectively. The timeliness of the two sequencing platforms was compared, and the Kappa consistency test was used to evaluate the consistency between the two sequencing platforms. Patients aged between 18 and 59 years with newly diagnosed acute myeloid leukemia (AML) underwent screening by rapid NGS combining multiplex RT-PCR and in situ fluorescence hybridization technique within 72 hours, from whom high-risk patients according to European LeukemiaNet (ELN) 2017 were screened for individualized induction therapy.Results:In terms of timeliness, the median time from sample receipt to report issuance were 3 (2, 4) days and 13 (11, 15) days under rapid NGS and conventional NGS testing, respectively, with a statistically significant difference ( Z=?22.636, P<0.001). Among 682 specimens with a total of 1 507 variants, rapid NGS detected a total of 1 499 variants, with a detection rate of 99.5% and 674 cases were accurate, with an accuracy rate of 98.8%; the conventional NGS detected 1 506 variants, with a detection rate of 99.9% and 681 cases were accurate, with an accuracy rate of 99.9%. In 682 specimens, there were 181 negative and 501 positive, in which 8 cases were missed under rapid NGS, and 1 case was missed under conventional NGS. The kappa value was 0.967 by Kappa consistency test, and P<0.001, suggesting good consistency and consistency between the two NGS platforms. From February 2021 to July 2022, 286 patients who were rapidly diagnosed of AML contained 78 patients screened as the ELN 2017 adverse-risk category, including 42 patients enrolled, with age 39 (33, 52) years old. After one cycle of venetoclax combined with decitabine induction therapy, 78.6%(38/42) of the patients achieved composite complete remission. Among the rest 104 additional myeloid neoplasms, rapid NGS detected mutations in 80 patients, with a detection rate of 76.9%, among which 89.0%(215/242) of the variants could serve as the basis for the diagnostic classification, prognostic evaluation, and target therapy of myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Conclusion:The rapid NGS based on targeted amplicon sequencing is in good consistency with conventional NGS, and shorters the diagnostic time, whose sensitivity and detection range meets the need for diagnostic classification, prognostic stratification, and target therapy of myeloid neoplasms.

Platelet-derived growth factor receptor beta (PDGFRB) rearrangements play an important role in the pathogenesis of eosinophilia-associated myeloid/lymphoid neoplasms. Up to now, more than 70 PDGFRB fusions have been identified. Here, a novel PDGFRB fusion gene CSNK2A1-PDGFRB has been identified in myeloproliferative neoplasm (MPN) with eosinophilia by RNA-sequencing, which has been verified by reverse transcription polymerase chain reaction and Sanger sequencing. The new PDGFRB fusion partner gene CSNK2A1 encoded one of the two catalytic subunit of casein kinase II (CK2). To our knowledge, this is the first report on the involvement of CSNK2A1 in fusion genes, especially fusion with another kinase PDGFRB in MPN. In addition, the CSNK2A1-PDGFRB fusion retained the entire kinase domain of PDGFRB and response to imatinib at low concentration. The patient with CSNK2A1-PDGFRB was sensitive to imatinib treatment and acquired sustained complete remission.

Objective:To evaluate the intestinal function in rats with exertional heat stroke (EHS) and explore the protective role of Ruifuping pectin (RFP) against heat related intestinal mucosal injury.Methods:One hundred and twenty healthy special pathogen free (SPF) male Sprague-Dawley (SD) rats were randomly divided into normothermic control group, EHS model group, hyperthermic plus drinking water group (H 2O+EHS group) and hyperthermic plus pectin group (RFP+EHS group) with 30 rats in each group. The rats in the H 2O+EHS group and RFP+EHS group were given water 20 mL/kg or RFP 20 mL/kg orally for 5 days during adaptive training period. After 1 week, the temperature control range was adjusted to (37±1)℃ using the temperature control treadmill, and the rat model of EHS was reproduced by one-time high temperature exhaustive exercise. No rehydration intervention was given during the training adaptation period in the EHS model group. The rats in the normothermic control group were maintained to room temperature (25±2)℃ and humidity (55±5)% without other treatment. Behavior tests including withdraw response, righting, and muscle strength were performed immediately after onset of EHS. Blood of inferior vena cava was collected, and the serum inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β, IL-10)] and activity of diamine oxidase (DAO) were detected by enzyme linked immunosorbent assay (ELISA). The intestinal mucosa was collected, after hematoxylin-eosin (HE) staining, and Chiu score was performed to assess EHS induced pathological changes under light microscope. Results:The rats in the EHS model group had behavioral, inflammatory and pathological changes, such as delayed withdraw response and righting, decreased forelimb pulling, increased inflammatory index, and obvious intestinal mucosal injury, which indicated that the reproduction of the EHS model was successful. There was no significant difference in above parameters between the H 2O+EHS group and the EHS model group except that the inflammatory index in the RFP+EHS group was improved. Compared with the EHS model group, the withdraw reflex to pain and righting after RFP pretreatment in the RFP+EHS group were significantly improved (righting score: 1.4±0.2 vs. 0.3±0.2, withdraw reflex to pain score: 1.0±0.1 vs. 0.2±0.1, both P < 0.05), the muscle strength was significantly increased (N: 13.0±0.5 vs. 8.2±0.6, P < 0.01). The levels of pro-inflammatory factors in the RFP+EHS group were significantly lower than those in the EHS model group [TNF-α (ng/L): 67.5±9.2 vs. 194.3±13.7, IL-6 (ng/L): 360.0±54.1 vs. 981.2±84.4, IL-1β (ng/L): 33.7±9.0 vs. 88.7±6.1, all P < 0.01], while the level of anti-inflammatory factor IL-10 was higher than that in the EHS model group (ng/L: 208.7±10.5 vs. 103.7±7.0, P < 0.01). The degree of intestinal mucosal injury in the RFP+EHS group was less severe than that in the EHS model group, and the Chiu score and DAO were significantly lower than those in the EHS model group [Chiu score: 1.5±0.2 vs. 3.8±0.0, DAO (U/L): 83.7±6.7 vs. 128.7±10.5, both P < 0.05]. Conclusions:High temperature training can damage the intestinal barrier function, and induce endotoxemia and systemic inflammatory response syndrome (SIRS) in rats. Oral prophylactic RFP can protect the intestinal barrier function, alleviate SIRS, and promote the recovery of basic nerve reflex and muscle strength after the occurrence of EHS in rats.

Platelet-derived growth factor receptor beta (PDGFRB) rearrangements play an important role in the pathogenesis of eosinophilia-associated myeloid/lymphoid neoplasms. Up to now, more than 70 PDGFRB fusions have been identified. Here, a novel PDGFRB fusion gene CSNK2A1-PDGFRB has been identified in myeloproliferative neoplasm (MPN) with eosinophilia by RNA-sequencing, which has been verified by reverse transcription polymerase chain reaction and Sanger sequencing. The new PDGFRB fusion partner gene CSNK2A1 encoded one of the two catalytic subunit of casein kinase II (CK2). To our knowledge, this is the first report on the involvement of CSNK2A1 in fusion genes, especially fusion with another kinase PDGFRB in MPN. In addition, the CSNK2A1-PDGFRB fusion retained the entire kinase domain of PDGFRB and response to imatinib at low concentration. The patient with CSNK2A1-PDGFRB was sensitive to imatinib treatment and acquired sustained complete remission.

Objective: To evaluate the effects of standardized management of hypertension on blood pressure control of hypertension patients with diabetes mellitus in workplace population. Methods: Taking the type and size of workplace into consideration, 61 work sites were selected in different provinces by using epidemiological field trial method. In each selected province, 2-4 work sites with similar economic and medical conditions were chosen, among which 1-3 were designated as the intervention group and the other one as the control group. In total, 443 patients with hypertension and diabetes mellitus were included, with 347 patients in the intervention group and 96 patients in the control group. After training, doctors conducted standardized management for patients in the intervention group for a period of 24 months, following up with them regularly once a month, and recorded changes in blood pressure, risk factors, target organ damage, and treatment, while the control group had no special intervention, and relevant information was collected only at baseline and 24 months. Blood pressure, blood pressure control rate, and blood glucose changes were compared between the two groups. Results: After receiving standardized management of hypertension, the control rate of hypertension for patients with both hypertension and diabetes mellitus in the intervention group increased from 24.2% to 63.7% (P<0.05) and the participants’ blood pressure also significantly decreased, by 10.2 (11.9-8.4) mmHg (1 mmHg=0.133 kPa) for systolic blood pressure and 7.7 (8.8-6.6) mmHg for diastolic blood pressure (P<0.05); moreover, the blood glucose also decreased slightly (P<0.001). In addition, the control rate of blood pressure increased to 63.7% with the increase of management time. In the control group, the control rate of hypertension increased to 46.9% (P<0.05) and the systolic and diastolic blood pressure decreased by 5.6 (8.9-2.2) and 4.5 (6.6-2.4) mmHg (P<0.05). Conclusions The standardized management of hypertension in the workplace can effectively reduce overall blood pressure levels and improve the control rate of hypertension in the working population.