Objective To investigate the influencing factors of hospitals to carry out hospital-enterprise collabora-tive innovation and improve the level of hospital-enterprise collaborative innovation.Methods Based on the method of rooted theory,open coding,main axis coding and selective coding were carried out on the contents of 30 in-depth interviews with experts,and pass the theoretical saturation test.Results The influencing factor model of hospitals participating in hospital-enterprise collaborative innovation was summarized.It includes 6 main categories,including cooperative income guarantee,market two-wheel drive,organization and management level,cooperative object and mode,main body innovation ability and enterprise technical support,which are divided into 3 dimen-sions:incentive factors,process factors and demand factors.Conclusion The enthusiasm of hospitals to carry out hospital-enterprise collaborative innovation needs to be improved,and the development of hospital-enterprise col-laborative innovation can be promoted from three aspects:focusing on the incentive effect of reasonable returns,encouraging high clinical value innovation activities,and improving the management level of collaborative innovation.

Objective To investigate the influencing factors of hospitals to carry out hospital-enterprise collabora-tive innovation and improve the level of hospital-enterprise collaborative innovation.Methods Based on the method of rooted theory,open coding,main axis coding and selective coding were carried out on the contents of 30 in-depth interviews with experts,and pass the theoretical saturation test.Results The influencing factor model of hospitals participating in hospital-enterprise collaborative innovation was summarized.It includes 6 main categories,including cooperative income guarantee,market two-wheel drive,organization and management level,cooperative object and mode,main body innovation ability and enterprise technical support,which are divided into 3 dimen-sions:incentive factors,process factors and demand factors.Conclusion The enthusiasm of hospitals to carry out hospital-enterprise collaborative innovation needs to be improved,and the development of hospital-enterprise col-laborative innovation can be promoted from three aspects:focusing on the incentive effect of reasonable returns,encouraging high clinical value innovation activities,and improving the management level of collaborative innovation.

Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

Objective:To investigate the clinical, laboratory, and prognostic features of myelodysplastic neoplasm (MDS) patients harboring acute myeloid leukemia (AML) -like mutations.Methods:We retrospectively analyzed clinical, molecular, and outcome data from 1 464 adults with primary MDS diagnosed at the Institute of Hematology and Blood Diseases Hospital from August 2016 to June 2024.Results:AML-like mutations were detected in 64 patients (4.4% ). Compared with patients without AML-like mutations, those with AML-like mutations were younger [median 50 ( IQR 39–60) vs 56 (45, 65) years; P=0.001], more often female (51.6% vs 35.4% ; P=0.009), had higher bone marrow blast percentage [6.5% (3.0%, 10.5% ) vs 2.5% (1.0%, 7.0% ) ; P<0.001], a higher rate of normal karyotype (75.0% vs 48.1% ; P<0.001), and lower hemoglobin levels [73 (67, 82) g/L vs 80 (66, 98) g/L; P=0.006]. The AML-like group had a higher number of gene mutations than the non-AML-like group [3 ( IQR 2–4) vs 2 (1, 3) ; P<0.001). It was enriched for mutations in NPM1, DNMT3A, WT1, PTPN11, NRAS, BCOR, FLT3, CEBPA, and MYC (all P<0.05) and had lower rates of U2AF1, ASXL1, and TP53 mutations (all P<0.05). Overall survival (OS) did not differ between groups ( P=0.730) ; however, the AML-like group had significantly shorter leukemia-free survival (LFS) [19 months (95% CI: 13–25) vs 46 months (95% CI: 38–54) ; P=0.012] and a higher 2-year cumulative incidence of AML transformation [ (41.7±9.1) % vs (10.4±1.1) % ; P<0.001]. Within the AML-like group, OS, LFS, and cumulative incidence of AML transformation did not differ between patients with low blasts and those with excess blasts (IB). Multivariable Cox regression identified age ≥60 years and PTPN11 mutations as independent adverse prognostic factors for OS, while DNMT3A, PTPN11, and FLT3 mutations independently predicted leukemic transformation. Conclusions:MDS patients harboring AML-like mutations exhibit distinct clinical and molecular features and a higher risk of progression to AML.

Objective:To explore the clinical features and molecular characteristics of myeloproliferative neoplasms (MPNs) patients with NFE2 gene mutations.Methods:Gene targeted sequencing was used to detect NFE2 gene mutation in 723 patients diagnosed with MPNs who were admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between April 2021 and June 2023. The association between NFE2 gene mutations and clinical features and molecular characteristics of MPNs patients were retrospectively analyzed.Results:Among 723 patients with MPNs, NFE2 gene mutations were found in 41 cases (5.7%) . NFE2 gene mutations were predominantly frameshift mutations (44.4%) , followed by nonsense mutations (33.3%) . The median number of mutations in patients with NFE2 gene mutations (4 [2,5]) was higher compared to the group without NFE2 gene mutations (2, [1,3]) ( P<0.001) . NFE2 gene mutations frequently co-occurred with mutations in MPL, ATM, PPM1D, and TET1. NFE2 gene mutations were mostly sub-clonal events, with 80.5% occurring after MPNs driver mutations (JAK2, CALR, or MPL) . NFE2 mutations were correlated with older age [median age: 60 (54, 67) years vs 54 (41, 63) years, P=0.001]. Patients with NFE2 gene mutations had a higher incidence of pre-diagnosis thrombosis (39.0% vs 22.0%, P=0.012) and pre-diagnosis arterial thrombosis (36.6% vs 20.4%, P=0.014) . Using a logistic regression analysis model adjusting for age and comorbidities (including chronic infections, malignancies, and autoimmune diseases) , NFE2 gene mutation was identified as an independent determinant of elevated tumor necrosis factor-alpha (TNF-α) ( OR=2.747, 95% CI: 1.143-6.605, P=0.024) , interferon-gamma (IFN-γ) ( OR=2.689, 95% CI: 1.191-6.076, P=0.017) , IL-10 ( OR=3.219, 95% CI: 1.343-7.717, P=0.009) , IL-12P70 ( OR=3.397, 95% CI:1.003-11.508, P=0.049) , IL-17 ( OR=2.284, 95% CI: 1.017-5.127, P=0.045) . In polycythaemia vera (PV) patients with the NFE2 gene mutation, the proportion of those classified as high-risk is notably higher in both the IWG-PV and mutation-enhanced international prognostic systems for PV (MIPSS-PV) (66.7% vs 25.3% for IWG-PV, P=0.033; 22.2% vs 2.0% for MIPSS-PV, P=0.013) . Similarly, for essential thrombocythaemia (ET) patients, the proportion in the high-risk group of the mutation-enhanced international prognostic systems for ET (MIPSS-ET) is significantly higher (15.4% vs 6.1%, P=0.021) . No statistically significant differences were observed in overall survival or cumulative incidence of thrombosis between NFE2-mutated (38 cases) and non-mutated MPNs patients (671 cases, P>0.05) . Conclusion:NFE2 gene mutations in MPNs were predominantly frameshift mutations. NFE2 gene mutations were correlated with older age, elevated levels of several inflammatory factors (including TNF-α、IFN-γ、IL-10、IL-12P70、IL-17) , and they mostly occurred in late-stage of MPNs.

Objective:To investigate the clinical, laboratory, and prognostic features of myelodysplastic neoplasm (MDS) patients harboring acute myeloid leukemia (AML) -like mutations.Methods:We retrospectively analyzed clinical, molecular, and outcome data from 1 464 adults with primary MDS diagnosed at the Institute of Hematology and Blood Diseases Hospital from August 2016 to June 2024.Results:AML-like mutations were detected in 64 patients (4.4% ). Compared with patients without AML-like mutations, those with AML-like mutations were younger [median 50 ( IQR 39–60) vs 56 (45, 65) years; P=0.001], more often female (51.6% vs 35.4% ; P=0.009), had higher bone marrow blast percentage [6.5% (3.0%, 10.5% ) vs 2.5% (1.0%, 7.0% ) ; P<0.001], a higher rate of normal karyotype (75.0% vs 48.1% ; P<0.001), and lower hemoglobin levels [73 (67, 82) g/L vs 80 (66, 98) g/L; P=0.006]. The AML-like group had a higher number of gene mutations than the non-AML-like group [3 ( IQR 2–4) vs 2 (1, 3) ; P<0.001). It was enriched for mutations in NPM1, DNMT3A, WT1, PTPN11, NRAS, BCOR, FLT3, CEBPA, and MYC (all P<0.05) and had lower rates of U2AF1, ASXL1, and TP53 mutations (all P<0.05). Overall survival (OS) did not differ between groups ( P=0.730) ; however, the AML-like group had significantly shorter leukemia-free survival (LFS) [19 months (95% CI: 13–25) vs 46 months (95% CI: 38–54) ; P=0.012] and a higher 2-year cumulative incidence of AML transformation [ (41.7±9.1) % vs (10.4±1.1) % ; P<0.001]. Within the AML-like group, OS, LFS, and cumulative incidence of AML transformation did not differ between patients with low blasts and those with excess blasts (IB). Multivariable Cox regression identified age ≥60 years and PTPN11 mutations as independent adverse prognostic factors for OS, while DNMT3A, PTPN11, and FLT3 mutations independently predicted leukemic transformation. Conclusions:MDS patients harboring AML-like mutations exhibit distinct clinical and molecular features and a higher risk of progression to AML.

Objective:To explore the outcome of sponge forceps assisted threading with Speedbridge technique for the treatment of acute closed Achilles tendon rupture.Methods:A retrospective case series study was conducted on 20 patients with acute closed Achilles tendon rupture treated in Zhengzhou Orthopedic Hospital from December 2019 to December 2021. There were 18 males and 2 females, with age range of 24-43 years [(29.5±7.6)years]. All patients were with unilateral injury, involving the left side in 13 patients and right side in 7. Examinations revealed a palpable defect in the Achilles tendon and positive Thompson test. A longitudinal incision was made at the medial edge of the ruptured tendon. Three nonabsorbable sutures were passed through the proximal stump with sponge forceps, bypassed the rupture site and fixed directly into the calcaneal bone. The disrupted tendon ends were aligned by the tendon-bundle technique using 4-0 absorbable sutures. The operation time and incision length were documented. The ankle joint range of motion (dorsiflexion/plantar flexion), American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Achilles tendon total rupture score (ATRS) in the affected and healthy side were compared at 3, 6 and 12 months postoperatively. The wound healing and complications were observed.Results:All patients were followed up for 12-16 months [(13.2±2.5)months]. The operation time was 40-66 minutes [(52.0±10.3)minutes], with the incision length of 3-4 cm [(3.3±0.7)cm]. In the affected side at 3 and 6 months postoperatively, the ankle joint dorsiflexion [(5.6±1.5)°, (10.5±0.2)°] and plantar flexion [(28.4±3.2)°, (33.5±1.5)°] showed statistically significant difference compared with the healthy side (all P<0.05). The ankle joint dorsiflexion [(13.9±0.7)°] and plantar flexion [(38.3±4.4)°] in the affected side were not statistically different from that of the healthy side at 12 months postoperatively (all P>0.05). The AOFAS ankle-hindfoot score was (58.3±5.4)points, (84.9±7.1)points and (91.8±6.3)points at 3, 6 and 12 months postoperatively, showing a gradual rise (all P<0.05). The ATRS was (60.5±4.9)points, (85.5±9.0)points and (93.1±5.7)points at 3, 6 and 12 months postoperatively, showing a gradual rise (all P<0.05). All incisions were healed primarily. No patients had wound infection, nerve injury or re-rupture. Pain at the anchor insertion site occurred in 2 patients at 1 month after operation and relieved after active functional rehabilitation at 4 months after operation. Transient pain at the Achilles tendon insertion occurred in 1 patient at 6 months after operation, and relieved after 2 weeks of oral non-steroidal anti-inflammatory drugs treatment. Conclusion:For acute closed Achilles tendon rupture, sponge forceps assisted threading with Speedbridge technique can attain short operation time, small incision and good functional recovery, with few complications.

Objective:To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) .Methods:From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done.Results:The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age ( P<0.001) , bone marrow blast percentage ( P<0.001) , bone marrow fibrosis ( P=0.046) , WHO classification ( P<0.001) , IPSS-R ( P<0.001) and IPSS-R karyotype group ( P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference ( P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation ( P=0.034) , DNMT3A mutation ( P=0.026) , NRAS mutation ( P=0.027) and NPM1 mutation ( P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups ( HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation ( HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation ( HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion:Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.

Objective:Diagnostic value assessment of sternal bone marrow cell morphology in patients with acquired hypocellular bone marrow failure syndromes (BMFS) characterized by normal cytogenetics.Methods:A total of 194 eligible patients with an acquired hypocellular BMFS pre-sternum diagnosis in Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College from June 2014 to January 2019 were reviewed. Sternal bone marrow evaluation was performed, and a post-sternum diagnosis was made. Clinical characteristics and overall survival (OS) were then compared among patients with different post-sternum diagnosis. Binary logistic regression was used to develop a predictive scoring system.Results:In 152 patients with pre-sternum AA diagnosis, 29 patients with a pre-sternum idiopathic cytopenia of undetermined significance (ICUS) diagnosis, and 13 patients with a pre-sternum clonal cytopenia of undetermined significance (CCUS) diagnosis, sternal bone marrow evaluation resulted in a change of diagnosis to hypocellular myelodysplastic syndrome (hypo-MDS) in 42.8% (65/152) , 24.1% (7/29) , and 30.8% (4/13) , respectively. Patients with a post-sternum hypo-MDS diagnosis showed a significant difference in OS compared with patients with a post-sternum AA diagnosis ( P=0.005) . Patients with ICUS/CCUS showed no difference in OS compared with AA and hypo-MDS ( P=0.095 and P=0.480, respectively) . A 4-item predictive scoring system to identify hypocellular BMFS patients that need sternal bone marrow evaluation was developed, including age > 60 years old ( OR=6.647, 95% CI 1.954-22.611, P=0.002, 2 points) , neutrophil alkaline phosphatase score ≤ 160 ( OR=2.654, 95% CI 1.214-5.804, P=0.014, 1 point) , abnormal erythroid markers evaluated by flow cytometry on iliac bone marrow ( OR=6.200, 95% CI 1.165-32.988, P=0.032, 2 points) , and DAT (DNMT3A, ASXL1, TET2) genes mutation ( OR=4.809, 95% CI 1.587-14.572, P=0.005, 1 point) . The Akaike information criterin (AIC) was 186.1. Conclusion:Patients with a pre-sternum acquired hypocellular BMFS diagnosis characterized by normal cytogenetics may not reach accurate diagnostic categorization without sternal bone marrow cell morphology evaluation, which could be considered a diagnostic tool for this patient population. A predictive scoring system was developed, and when the total score is ≥ 2 points, sternal bone marrow evaluation should be performed for accurate diagnostic categorization that is critical to optimal patient care.

Objective:To explore predictors of overall survival (OS) in Chinese patients with polycythemia vera (PV) .Methods:A total of 906 consecutive newly diagnosed patients with PV seen at the Blood Diseases Hospital, Chinese Academy of Medical Sciences, from June 2007 to February 2020 were included, and their data were collected. PV was diagnosed according to 2016 World Health Organization (WHO) diagnostic definitions. OS and prognostic factors were retrospectively analyzed.Results:Among the 906 patients, 439 were male (48.5%) and 467 were female (51.5%) . The median age was 57 years (range: 18-91 years) . 31.6% (276/874) of the patients had a thrombosis history at diagnosis, and 4.6% (25/541) of the patients had abnormal cytogenetics. The median follow-up was 54 months (95% confidence interval [ CI] 8-130 months) . The 5- and 10-year cumulative deaths were 5.8% (95% CI 4.8%-6.7%) and 11.1% (95% CI 9.3%-12.9%) , respectively. Univariate analysis showed that age ≥60 years, thrombosis history, white blood cells (WBC) ≥15×10 9/L, platelet (PLT) ≥450×10 9/L, and platelet distribution width (PDW) ≥15 fl significantly correlated with worse OS, and palpable spleen correlated with better OS. Multivariate analysis showed that age ≥60 years ( HR=4.3, 95% CI 2.1-9.2, P<0.001) and PDW ≥15 fl ( HR=2.1, 95% CI 1.1-4.0, P=0.023) were independent prognostic factors for worse OS. The 5-year cumulative death for patients with PDW ≥15 fl or PDW<15 fl was 8.6% (95% CI 5.9%-11.3%) or 4.4% (95% CI 3.4%-5.4%) , respectively. The 5-year cumulative death for patients defined as low-, intermediate-, and high-risk patients by international working group score system for PV (IWG-PV) were 0.8% (95 CI 0.2%-1.4%) , 4.0% (95% CI 2.7%-5.3%) , and 12% (95% CI 9.6%-14.4%) , respectively, with a significant difference among the three cohorts ( P<0.05) . PDW ≥ 15 fl significantly affected OS for intermediate- and high-risk patients ( HR=2.3, 95% CI 1.2-4.2, P=0.009) defined by IWG-PV score system, but not for low-risk patients ( HR=3.1, 95% CI 0.2-52.0, P=0.405) . Conclusions:Age ≥60 years and PDW ≥15 fl were independent prognostic factors for worse OS in PV. IWG-PV score system effectively predicted OS for Chinese patients with PV.