Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

Objective:To evaluate the role of P2X4 receptor (P2X4R) in the maintenance of trigeminal neuralgia and the relationship with p38 mitogen-activated protein kinase (p38 MAPK)/brain-derived neurotrophic factor (BDNF) signaling pathway in rats.Methods:Forty-eight clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), trigeminal neuralgia+ dimethylsulfoxide (DMSO) group (TN+ DMSO group), and trigeminal neuralgia+ P2X4R specific antagonist 5-BDBD group (TN+ 5-BDBD group). The model was developed by chronic constriction of the infraorbital nerve. The infraorbital nerve was only exposed without ligation in group S. At 3, 7, 10 and 14 days after developing the model, 5 μg/μl 5-BDBD 10 μl was intrathecally injected in TN+ 5-BDBD group, and 2% DMSO 10 μl was intrathecally injected in TN+ DMSO group. The facial mechanical pain withdrawal threshold (MWT) was measured at 1 day before developing the model and 1, 3, 7, 10, 14 and 28 days after developing the model (T 0-6). The rats were sacrificed and the trigeminal ganglia were taken for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the MWT was significantly decreased at T 1-6, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in TN group ( P<0.05). Compared with TN group, the MWT was significantly increased at T 3-6, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in TN+ 5-BDBD group ( P<0.05), and no significant change was found in the indexes mentioned above in TN+ DMSO group ( P>0.05). Conclusions:P2X4R is involved in the maintenance of trigeminal neuralgia in rats, which may be related to the activation of p38 MAPK/BDNF signaling pathway and the increase in inflammatory mediator release.

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*

Objective:To summarize the clinical features, treatments and outcomes of patients with SMARCB1(INI-1)-deficient sinonasal carcinoma (SDSC).Methods:Fifteen patients who were diagnosed as SDSC in Beijing Tongren Hospital from October 2016 to June 2021 were retrieved, including nine males and six females, ranged from 25 to 78 years old. For TNM stage, one case was in stage T2, one case was in stage T3, 13 cases were in stage T4; 13 cases were in stage N0, two cases were in stage N2; 14 cases were in stage M0, one case was in stage M1. The most common paranasal sinus affected by tumor was the ethmoid sinus. Five patients were treated by radical surgical resection combined with postoperative adjuvant therapy, four patients treated by neoadjuvant therapy with surgical resection, three patients treated by surgical resection only, one patient treated by neoadjuvant therapy with concurrent chemoradiotherapy, one patient treated by preoperative radiotherapy with surgery, and one patient received palliative chemotherapy. Immunohistochemical analysis was performed in all cases. The Kaplan-Meier method was used to draw the survival curve, and the Log-rank test was used to compare the difference to 20 undifferentiated carcinoma patients with positive INI-1 expression in the same period.Results:Immunohistochemical analysis showed the complete absence of INI-1 expression in the tumor nuclei in all 15 cases. The follow-up information was available with a median follow-up time of 21 months (3-56 months). The 3-year overall survival rate, disease specific survival rate, disease-free survival rate and metastasis-free survival rate were 58.9%, 58.9%, 36.4% and 31.2%, respectively. Disease-free survival in SDSC patients was significantly lower compared with undifferentiated carcinoma patients with positive INI-1 expression ( HR=2.87,95% CI:0.92~8.91, P=0.043). Cox regression analysis showed that patients with comprehensive treatment based on surgery had a better prognosis than others ( HR=8.61,95% CI:1.38~53.73, P=0.021). Conclusion:SDSC is a highly aggressive malignant tumor with the characteristics of easy recurrence, early metastasis and poor prognosis. INI-1 immunohistochemical analysis is recommended in the pathologically poorly differentiated sinonasal carcinoma. Comprehensive treatment based on radical resection may be the first choice for SDSC patients.

Objective:To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases.Methods:From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin's lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) .Results:① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups ( P=0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups ( P>0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs. (94.77±1.75) % , P=0.004; (91.45±2.63) % vs. (95.54±2.05) % , P=0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs. (95.08±1.41) % , P=0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively ( P=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs. 27.41% , respectively, among those over 35 (40.07±6.65) % vs. (27.41±4.54) % ( P=0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs. (95.08±0.95) % , P=0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs. (94.49±1.45) % , P=0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs. (95.62±1.26) % , P=0.404]. Conclusion:The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.

Background: Endoscopic submucosal dissection (ESD) has become the preferred treatment of early colorectal cancer. PDCD4 and autophagy have important clinical significance in the pathogenesis of colorectal cancer. Aims: To explore the expressions and significance of apoptosis factor PDCD4 and autophagy factors LC3Ⅱ and p62 in colorectal cancer. Methods: Fifty-four early colorectal adenocarcinoma patients treated by ESD from Jan. 2015 to Nov. 2020 at Binzhou Medical University Hospital were collected. The expressions of PDCD4, LC3Ⅱ and p62 were detected by immunohistochemistry, and the correlations with clinicopathological factors were analyzed. The differential expression of PDCD4 in pan-cancer was analyzed by bioinformatics analysis. Results: Expression of PDCD4 was associated with the long-diameter of paracancer adenoma (P<0.05), and expressions of LC3Ⅱ and p62 were associated with the long-diameters of adenocarcinoma and paracancer adenoma (P<0.05). The positive expression of PDCD4 in P-NIMM was located in the nucleus, while the positive expression in adenocarcinoma was located in cytoplasm. The nucleus/cytoplasm ratio of PDCD4 was significantly higher in P-NIMM than in P-LGIN, P-HGIN and adenocarcinoma (P<0.05), and the nucleus/cytoplasm ratio of PDCD4 was significantly higher in P-LGIN, P-HGIN than in adenocarcinoma (P<0.05). The positive expression rates of LC3Ⅱ and p62 were significantly higher in adenocarcinoma than in P-NIMM and P-LGIN (P<0.05). In P-LGIN, P-HGIN and adenocarcinoma, the expression of PDCD4 was negatively correlated with the expressions of LC3Ⅱ and p62 (P<0.05). The bioinformatics analysis showed that expression of PDCD4 was significantly reduced in a variety of malignant tumors including colorectal cancer (P<0.05). Conclusions: The inhibition of apoptosis and activation of autophagy may promote the occurrence of colorectal cancer, and its mechanism may be related to the intracellular transposition of PDCD4 that inhibits cell apoptosis and enhances autophagy, and activating cellular autophagy may further accelerate the degradation of PDCD4 and thus reducing its cancer inhibiting effect.

Objective:To investigate the risk factors for death in patients with corona virus disease 2019 (COVID-19).Methods:The clinical data of 141 cases of patients diagnosed with COVID-19 at Renmin Hospital of Wuhan University from February 1 to February 26, 2020 were included in this retrospective analysis. The gender, age, time of hospitalization after the onset, clinical manifestations, underlying diseases, laboratory examination indicators (inculding white blood cell counts, neutrophil counts, lymphocyte counts, lymphocyte subsets, immunoglobulin, complement 3, complement 4, D-dimer, fibrinogen), and short term prognosis were compared between the death group and the survival group. Logistic regression was used to analyze the factors influencing the death of COVID-19 patients. The t test, Mann Whitney U test or chi-square test were used for comparison between groups. Results:Of the 141 COVID-19 patients, 52 died and 89 survived. The age, hypertension, chronic respiratory diseases, cardiovascular and cerebrovascular diseases, fever and wheeze of patients in the death group were all higher than those in the survival group, which were (70.7±13.3) years old vs (50.4±15.3) years old, 51.9%(27/52) vs 14.6%(13/89), 15.4%(8/52) vs 4.5%(4/89), 30.8%(16/52) vs 7.9%(7/89), 80.8%(42/52) vs 61.8%(55/89) and 50.0%(26/52) vs 25.8%(23/89), respectively. The differences were all statistically significant ( t=7.972, χ2=22.104, 3.615, 12.392, 5.503 and 8.447, respectively, all P<0.05). The white blood cell count, neutrophil count, CD4 + /CD8 + T lymphocyte, immunoglobulin E, D-dimer, fibrinogen, CD19 + T lymphocyte proportion and CD19 + T lymphocyte count of patients in the death group were all higher than those in the survival group, which were 8.20(5.26, 13.01)×10 9/L vs 5.29(3.96, 7.04)×10 9/L, 7.40(4.54, 11.46)×10 9/L vs 3.16(2.20, 5.01)×10 9/L, 2.32(1.77, 3.11) vs 1.63(1.25, 2.08), 125.0(42.6, 275.0) IU/mL vs 66.8(38.3, 143.0) IU/mL, 7.27(2.11, 16.21) mg/L vs 0.95(0.38, 2.54) mg/L, 4.37(2.72, 6.78) g/L vs 4.10(2.78, 4.97) g/L, (23.19±13.43)% vs (15.38±6.38)%, and (181.5±115.4)/μL vs (98.89±77.64)/μL, respectively. The differences were all statistically significant ( Z=3.944, 4.210, 2.834, 1.190, 5.497, 1.180, t=3.987, 3.411, respectively, all P<0.05). The lymphocyte count, CD3 + T lymphocyte proportion, CD3 + T lymphocyte count, CD8 + T lymphocyte proportion, CD8 + T lymphocyte count, CD16 + CD56 + T lymphocyte count and CD4 + T lymphocyte count were all lower than those in survival group, which were 0.47(0.37, 0.96)×10 9/L vs 1.33(0.90, 1.55)×10 9/L, 48.72%(42.31%, 76.92%) vs 69.91%(65.05%, 75.36%), 223.0(100.0, 403.0)/μL vs 761.0(499.0, 1 092.0)/μL, 13.82%(10.32%, 19.82%) vs 24.90%(20.87%, 29.57%), 55.5(30.5, 106.0)/μL vs 318.0(162.5, 443.5)/μL, 63.0(29.0, 99.5)/μL vs 140.0(69.5, 195.5)/μL and (209.74±140.13)/μL vs (487.61±232.02)/μL, respectively. The differences were all statistically significant ( Z=6.937, 3.944, 5.883, 3.924, 5.703, 3.517 and t=7.558, respectively, all P<0.01). Age, history of hypertension, white blood cell count, D-dimer, and fibrinogen were the risk factors for death of COVID-19 (odds ratio ( OR)=1.170, 10.405, 3.055, 1.128 and 1.343, respectively, all P<0.05). Conclusion:Age, underlying hypertension, white blood cell count, D-dimer and fibrinogen are independent prognostic factors for COVID-19.

Objective: To analyze the differentially expressed genes related to the chemosensitivity with the TPF regimen for hypopharyngeal squamous cell carcinoma and to measure potential functional targeting genes expressions. Methods: Twenty-nine patients with primary hypopharyngeal cancer who underwent induction chemotherapy with TPF from January 2013 to December 2017 in Beijing Tongren Hospital were enrolled for microarray analysis, including 28 males and 1 female, aged from 43 to 73 years old. Among them, 16 patients were sensitive to chemotherapy while 13 patients were non-sensitive. Illumina Human HT-12 Bead Chip was applied to analyze the gene expressions and online bioinformatics analysis was used to analyze the differentially expressed genes. Reverse transcription and quantitative real-time PCR (RT-qPCR) was used to measure the mRNA expression of potential functional genes of TPF induction chemotherapy in 43 samples, 29 from original patients and 14 from additional patients. Graphpad prism 7.0 software was used for statistical analysis. Results: A total of 1 381 significantly differentially expressed genes were screened out. By GO analysis, up-regulated genes included sequestering in extracellular matrix, chemokine receptor binding and potassium channel regulator activity; down-regulated genes included regulation of angiogenesis, calcium ion binding and natural killer cell activation involved in immune response. With KEGG database analysis, down-regulated pathways included ECM-receptor interaction and peroxisome and up-regulated pathways included Glutathione metabolism and PPAR signaling pathway. The expressions of CD44 and IL-6R were significantly different and appeared biologically significant. CD44 was significantly upregulated in insensitive tissues (0.54±0.06) compared with sensitive tissues (0.33±0.04)(P<0.01). IL-6R was significantly downregulated in insensitive tissues (0.44±0.03) compared with sensitive tissues. (0.68±0.03) (P<0.01). Conclusion CD44 and IL-6R may be potentially functional genes of TPF induction chemotherapy in hypopharyngeal squamous cell carcinoma.

Objective:To evaluate the application of computer-assisted design and three-dimensional printing technique in reconstruction of maxillary defects with individual free fibular flap.Methods:A total of 13 patients, 7 males and 6 females with age from 12 to 55 years old, underwent the reconstruction of maxillary defects after subtotal or total maxillectomy for benign or malignant tumors between January 2016 and December 2018 were reviewed. Ther were 4 cases of subtotal maxillectomy and 9 cases of total maxillectomy. Before operation, osteotomy line was planned on three-dimensional images. A three-dimensional individual resin fibula model based on mirror images of the healthy side maxilla was obtained to fabricate an anatomically adapted osteomyocutaneous fibula free flap using computer-assisted design and forming. Oral, nasal, and eye functions and facial appearance were evaluated.Results:The 13 cases were followed up for 5-40 months, all flaps were alive except one due to flap failure and all cases were tumor free confirmed by CT or MRI. Ten patients could eat normal food without nasal food return, and 3 cases had palatal fistula. Eleven cases showed good speaking functional results. All cases had normal eye positions, no cases with diplopia and loss of vision. With evaluation by VAS, an average score of 8 was obtained, and most of patients were satisfied with their postoperative facial appearances.Conclusion:Reconstruction of maxillary defects by free fibular flap designed by three-dimensional printing and computer-assisted technique not only restored oral, nasal and eye functions, but also showed satisfactory facial appearance.

Objective:To evaluate clinical applications and efficacy of submental artery perforator flap in reconstruction surgery after removal of pharyngeal carcinoma.Methods:A total of 27 patients in the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University were included, 23 males and 4 females with age from 40 to 70 years old, and 17 patients were hypopharyngeal carcinoma (HPC) and 10 patients were oropharyngeal carcinoma (OPC). All patients underwent tumor resection followed by simultaneously reconstruction surgery using submental artery perforator flap between January 2015 and December 2019. Of 5 patients with palatine tonsil cancer, 4 underwent the combined approach of neck and oral resection and 1 with madibulotomy. All 5 patients with tongue base cancer received transhyoid partial glossotomy with or without partial laryngectomy. Sixteen patients with pyriform sinus carcinoma received partial laryngo-pharyngectomy with preservation of laryngeal functions. One patient with posterior hypopharyngeal wall carcinoma had partial pharyngectomy. Prognosis and laryngeal functions were analyzed after reconstruction surgery with submental artery perforator flap in patients with pharyngeal carcinoma.Results:The 27 patients were followed up for 6-66 months, with a median of 13 months, of them 24 patients were alive without recurrence or metastasis, 1 patient died of recurrence, 1 patient died of esophageal carcinoma and 1 patient was alive with the recurrence of tongue base carcinoma. Postoperative complications included flap failure for 1 case, pharyngeal fistula for 1 case, subcutaneous hydrops for 2 cases and lymphatic fistula for 1 case. Total 2 and 3 year survival rates were 92.9% and 88.9%, respectively. Total decanulation rate was 92.6%; decanulation rate and intubation time were 16/17 and 3.5 months in HPC patients; and decanulation rate and intubation time were 9/10 and 2 months in OPC patients. Total oral feeding rate was 92.6% and nasogastric feeding time was 3.5 weeks in HPC patients and 3 weeks in OPC patients.Conclusion:The submental artery perforator flap is an excellent choice for reconstruction surgery after removal of oropharyngeal and hypopharyngeal carcinoma, with good outcomes of laryngeal functions.